TuberculosisPhase 2NCT05077813
Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for Treating Patients With Multidrug-resistant TB and Patient With Both Multidrug-resistant TB and COVID-19
A Phase 2 study testing 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB), 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) and All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) in people with Tuberculosis, run by Kafrelsheikh University at 2 sites in 2 countries.
Trial summary
Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for treating patients with Multidrug-resistant TB and patient with both Multidrug-resistant TB and COVID-19 . Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB), 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) and All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2021to Feb 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age above 18 up to 65 years
- Microbiologically or histologically confirmed active tuberculosis as well as confirmed positive with COVID-19
- Clinically confirmed latent tuberculosis
- Drug resistant MTb
- Negative pregnancy test for 18-40 year-old females
- Able to sign consent
Who cannot join
- HIV positive
- Known intolerance of vitamin D
- Sarcoidosis
- Hyperparathyroidism or nephrolithiasis
- Taking vitamin D or A supplementation in the two months preceding enrolment
- Baseline serum corrected calcium >2.65 mmol/L
Show all 23Show fewer
- Current haemodialysis
- Children, pregnant or breastfeeding individuals
- Concomitant benzothiadiazine derivative, cardiac glycoside, carbamazepine, phenobarbital, phenytoin, primidone or long-term immunosuppressant therap
- Extra-pulmonary or smear negative tuberculosis
- Patients receiving steroids, cytotoxic drugs, post transplant or metastatic malignancy, or not expected to survive for the duration of ATT
- Pregnant or lactating women
- Active diarrhoea, indicating possible fat-soluble vitamin malabsorption.
- Baseline Hypercalcemia >10.5 mg/dl
- Concurrent use of cyclosporin, cisplatin, amfotericin B, cephalosporins, polymyxins and vancomycin.
- History of adverse events on previous Minocycline or other tetracycline use (by spontaneous reporting nor by active questioning).
- Depressive disorder
- Body mass index less than 18 points or higher than 25 points
- Contraindications for hormonal contraception or intrauterine device.
- Autoimmune diseases A history of organ, bone marrow or hematopoietic stem cell transplantation
- Patients receiving anti-hcv treatment
- Permanent blindness in one eye
- History of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Saudi Arabia1 site
Ministry of health. First health cluster
Riyadh, Riaydh, 12221
About this study
Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for treating patients with Multidrug-resistant TB and patient with both Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study
I)Part of Tuberculosis
Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden , stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge . New drug discovery could require several years with no guarantee but repurposing established may be useful to treat patients with tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline , and vitamin D as a novel quadrate therapy against TB.Drug-resistant tuberculosis represents a global emergency, requiring new drugs. Recently Minocycline was found to be highly potent in laboratory strains of Mycobacterium TB, and 30 drug-sensitive and multidrug/extensively drug-resistant clinical strains were susceptible to clinically attainable dosages. The lung concentration-time profiles of a 7 mg/kg/day human-equivalent minocycline dosage yielded bacterial kill rates comparable to first-line antituberculosis drugs. Extracellular bacilli were destroyed directly by minocycline. Minocycline also killed intracellular bacilli indirectly through granzyme A-driven apoptosis. Furthermore, minocycline showed dose-dependent antiinflammatory effect, suggesting that it may protect tuberculosis patients against immunopathology. A study showed that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing . A recent study showed that Minocycline-induced significantly inhibition of IDO expression. But Minocycline-induced inhibition of IDO expression is retinoid-dependent. The combined treatment with minocycline and retinol, however, resulted in a striking, statistically significant decrease in IDO. Co-treatment with minocycline and retinol again resulted in decreased TNF-α and IL-6 levels. A study showed that IL-6 inhibits IFN-γ induced autophagy in Mycobacterium (TB) H37Rv infected macrophages. As well as neutralization of endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-γ mediated killing of the intracellular bacteria. Minocycline's anti-inflammatory effects are mediated through RAR signaling. Therefore, The combined treatment with minocycline and retinol is expected to effectively inhibit (TB) and its inflammatory complication, Fortunately, Retinoic Acid significantly inhibits the in vivo growth of M. tuberculosis and the development of tuberculosis. In addition to, 13-Cis RA and Chicoric Acid ( CA ) enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. Moreover, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly . Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA . Therefore we will use retinoic acid to induce the effect of Minocycline as well as its ability to inhibit tuberculosis in combination with CA .Recent data showed that Vitamin D support innate immune responses to Mycobacterium TB and Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis. Deficiency of vitamin D has long been implicated in activation of (TB) . Serum vitamin D in TB patients are lower than in healthy controls . Vitamin D has been found to speed up the clearance of (TB) bacteria from the lungs of people with multi-drug resistant TB, according to a study of 1,850 patients. It was showed that Vitamin D receptor (VDR) must form a heterodimer complex with retinoid X receptor (RXR) to regulate gene transcription. Retinol plays a crucial role in lung development and signaling the vitamin D pathway. 9-cis-retinoic acid, an active vitamin A metabolite and the ligand of RXR, assists VDR signaling and suppresses the degradation of circulating vitamin D.
Read the detailed description
This double blinded, randomized, placebo controlled trial on the clinical efficacy and antimicrobial mechanisms of quadrate therapy(Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D) as a Potent Quadrate Therapy Against Tuberculosis. 200 men and women will be enrolled , who are age 18 to 65 years inclusive, have at least two positive sputum smears for tuberculosis (TB), and have given informed consent to participate in the study. All of the enrollees will have active TB . The effect of the quadrate therapy status will be examined in the context of a randomized trial conducted in Egyptian or Saudi Arabian Subjects will be randomized to receive either the quadrate therapy or placebo from the start of their TB therapy, through the 1 months of anti-TB therapy, and until the last recruited patient reaches 6 months of follow up. Thus, the first subject is likely to be followed for 12 months, assuming the duration of recruitment is 12 months. The endpoints of interest include bacteriologic cure, immune response parameters, and clinical outcomes. The researchers will also examine the utility of these immune response parameters as surrogate markers for treatment efficacy in TB, irrespective of the quadrate therapy and other risk factors. The study will be carried out as a collaborative effort between. Kafr elshiekh university ,Faculty of Medicine, Egypt and First health cluster ,Ministry of health ,Saudia Arabia. Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid or All trans retinoic acid or 9 cis retinoic acid gradual in 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid .Chicoric acid (also known as cichoric acid and dicaffeoyltar- taric acid) is the main phenolic compound found in Echinacea purpurea. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets Caffeic acid derivative levels are typically as follows: caftaric acid = 0.5 to 2.0 mg/tablet; cichoric acid = 3.4 to 8.5 mg/tablet; chlorogenic acid = < 0.5 mg/tablet; dicaffeoyl quinic acids (including cynarin) = 0.7 to 2.0 mg/tablet; echinacoside = 1.0 to 1.7 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 (b) placebo. The primary objectives are to: (1) determine the efficacy of the quadrate therapy on sputum and culture negativity at one month and two months; (2) determine the efficacy of micronutrient supplements on survival between two arms at 8 and 24 months; and (3) determine the efficacy of micronutrient supplements on TB relapse and reinfection. Secondary study objectives are to: (1) compare the treatment arms with respect to absolute change in CD4 counts from 0 to 1, 6, 12 months; (2) compare the treatment arms with respect to weight change from baseline and1 months, 6 months, and 12 months; (3) compare the treatment arms with respect to immunological parameters, namely ex vivo lymphocyte proliferation; and cytokine production, namely IL-2, IL-6, INF-g INF-Alpha, IL-12, and TNF-a, and Interferon alpha at 1, 6, 12 months; and (4) correlate the above mentioned immunological markers with smear conversion rates at 1 month, 2 months, cure, relapse, and death. Finally, we suggest that this combination therapy will effectively inhibit tuberculosis infection and achieve treatment with significant effect against (TB)
- Conditions
- Tuberculosis
- Being tested
- 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB), 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB), All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB), All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB), 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB)Combination product
- Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4
9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB)Combination product
- Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 9 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4
All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB)Combination product
Active Comparator: All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D 50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4
All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)Combination product
50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4
13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)Combination product
50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4
The standard therapyOther
The standard therapy 100 infected patients with confection of COVID-19 and MDR-TB will receive the standard therapy for tuberculosis for 30 days
| Study group | Role | What they receive |
|---|---|---|
| 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) | Active comparator | 50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 Receives: Combination Product: 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) |
| 9 cis retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) | Active comparator | 50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 9 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 Receives: Combination Product: 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) |
| All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) | Active comparator | 50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 Receives: Combination Product: All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) |
| 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) | Active comparator | 50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 Receives: Combination Product: 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) |
| All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) | Active comparator | 50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 Receives: Combination Product: All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) |
| The standard therapy | Placebo comparator | The standard therapy 100 infected patients with confection of COVID-19 and MDR-TB will receive the standard therapy for tuberculosis for 30 days 50- 50- Receives: Other: The standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first negative SARS-CoV-2 PCR in NP swap and Mycobacterium tuberculosis sputum culture
Measured: within 4 weeks
Secondary outcomes (10)
Sputum culture result (positive or negative)& COVID-19 PCR (positive or negative)
Measured: 2 weeks after therapy start date
Serum levels of CRP and ESR
Measured: one month
All cause mortality rate
Measured: one month
Absolute lymphocyte counts (CD4,CD8 and CD25+FOXP3+ Regulatory T)
Measured: one month
Measurement of cytokine (IFN-gamma and alpha , IL-6, IL-10, TNF-alpha, TGF-beta) levels produced in response to M. tb.
Measured: one month
Vitamin D status
Serum 25(OH)D concentrations
Measured: one month
Retinoic acid status
Serum Retinoic acid concentrations
Measured: one month
Minocycline status
Serum Minocycline concentrations
Measured: one month
Serum indoleamine 2,3-dioxygenase (IDO) enzyme status
Serum indoleamine 2,3-dioxygenase (IDO) enzyme concentration
Measured: one month
Chicoric Acid status
Serum Chicoric Acid concentrations
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2021
- Study startDec 2021 (estimated)
- Primary completionFeb 2022 (estimated)
- Study completionFeb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Kafrelsheikh UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kafrelsheikh University
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Saudi Arabia
- Responsible party
- Principal investigator, Mahmoud Ramadan mohamed Elkazzaz, Kafrelsheikh University
- Investigators
- Dr Mahmoud R Elkazzaz, M.Sc of Biochemistry, Principal investigator, Faculty of Science , Damietta UniversityAmr K Ahmed, Principal investigator, Ministry of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05077813
- Sponsor's protocol ID
- How to kill Tuberculosis
- Status last verified
- Oct 2021
- First submitted
- 10 Oct 2021
- Last updated
- 14 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for Treating Patients With Multidrug-resistant TB and Patient With Both Multidrug-resistant TB and COVID-19
- ClinicalTrials.gov ID
- NCT05077813
- Acronym / sponsor ID
- How to kill Tuberculosis
- Conditions
- Tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Kafrelsheikh UniversityUniversity, hospital or other
- Collaborators
- Ministry of Health, Saudi Arabia
- Study start
- Dec 2021 (estimated)
- Primary completion
- Feb 2022 (estimated)
- Study completion
- Feb 2022 (estimated)
- First posted
- 14 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for treating patients with Multidrug-resistant TB and patient with both Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study
I)Part of Tuberculosis
Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden , stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge . New drug discovery could require several years with no guarantee but repurposing established may be useful to treat patients with tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline , and vitamin D as a novel quadrate therapy against TB.Drug-resistant tuberculosis represents a global emergency, requiring new drugs. Recently Minocycline was found to be highly potent in laboratory strains of Mycobacterium TB, and 30 drug-sensitive and multidrug/extensively drug-resistant clinical strains were susceptible to clinically attainable dosages. The lung concentration-time profiles of a 7 mg/kg/day human-equivalent minocycline dosage yielded bacterial kill rates comparable to first-line antituberculosis drugs. Extracellular bacilli were destroyed directly by minocycline. Minocycline also killed intracellular bacilli indirectly through granzyme A-driven apoptosis. Furthermore, minocycline showed dose-dependent antiinflammatory effect, suggesting that it may protect tuberculosis patients against immunopathology. A study showed that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing . A recent study showed that Minocycline-induced significantly inhibition of IDO expression. But Minocycline-induced inhibition of IDO expression is retinoid-dependent. The combined treatment with minocycline and retinol, however, resulted in a striking, statistically significant decrease in IDO. Co-treatment with minocycline and retinol again resulted in decreased TNF-α and IL-6 levels. A study showed that IL-6 inhibits IFN-γ induced autophagy in Mycobacterium (TB) H37Rv infected macrophages. As well as neutralization of endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-γ mediated killing of the intracellular bacteria. Minocycline's anti-inflammatory effects are mediated through RAR signaling. Therefore, The combined treatment with minocycline and retinol is expected to effectively inhibit (TB) and its inflammatory complication, Fortunately, Retinoic Acid significantly inhibits the in vivo growth of M. tuberculosis and the development of tuberculosis. In addition to, 13-Cis RA and Chicoric Acid ( CA ) enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. Moreover, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly . Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA . Therefore we will use retinoic acid to induce the effect of Minocycline as well as its ability to inhibit tuberculosis in combination with CA .Recent data showed that Vitamin D support innate immune responses to Mycobacterium TB and Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis. Deficiency of vitamin D has long been implicated in activation of (TB) . Serum vitamin D in TB patients are lower than in healthy controls . Vitamin D has been found to speed up the clearance of (TB) bacteria from the lungs of people with multi-drug resistant TB, according to a study of 1,850 patients. It was showed that Vitamin D receptor (VDR) must form a heterodimer complex with retinoid X receptor (RXR) to regulate gene transcription. Retinol plays a crucial role in lung development and signaling the vitamin D pathway. 9-cis-retinoic acid, an active vitamin A metabolite and the ligand of RXR, assists VDR signaling and suppresses the degradation of circulating vitamin D.
Detailed description
This double blinded, randomized, placebo controlled trial on the clinical efficacy and antimicrobial mechanisms of quadrate therapy(Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D) as a Potent Quadrate Therapy Against Tuberculosis. 200 men and women will be enrolled , who are age 18 to 65 years inclusive, have at least two positive sputum smears for tuberculosis (TB), and have given informed consent to participate in the study. All of the enrollees will have active TB . The effect of the quadrate therapy status will be examined in the context of a randomized trial conducted in Egyptian or Saudi Arabian Subjects will be randomized to receive either the quadrate therapy or placebo from the start of their TB therapy, through the 1 months of anti-TB therapy, and until the last recruited patient reaches 6 months of follow up. Thus, the first subject is likely to be followed for 12 months, assuming the duration of recruitment is 12 months. The endpoints of interest include bacteriologic cure, immune response parameters, and clinical outcomes. The researchers will also examine the utility of these immune response parameters as surrogate markers for treatment efficacy in TB, irrespective of the quadrate therapy and other risk factors. The study will be carried out as a collaborative effort between. Kafr elshiekh university ,Faculty of Medicine, Egypt and First health cluster ,Ministry of health ,Saudia Arabia. Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid or All trans retinoic acid or 9 cis retinoic acid gradual in 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid .Chicoric acid (also known as cichoric acid and dicaffeoyltar- taric acid) is the main phenolic compound found in Echinacea purpurea. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets Caffeic acid derivative levels are typically as follows: caftaric acid = 0.5 to 2.0 mg/tablet; cichoric acid = 3.4 to 8.5 mg/tablet; chlorogenic acid = < 0.5 mg/tablet; dicaffeoyl quinic acids (including cynarin) = 0.7 to 2.0 mg/tablet; echinacoside = 1.0 to 1.7 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 (b) placebo. The primary objectives are to: (1) determine the efficacy of the quadrate therapy on sputum and culture negativity at one month and two months; (2) determine the efficacy of micronutrient supplements on survival between two arms at 8 and 24 months; and (3) determine the efficacy of micronutrient supplements on TB relapse and reinfection. Secondary study objectives are to: (1) compare the treatment arms with respect to absolute change in CD4 counts from 0 to 1, 6, 12 months; (2) compare the treatment arms with respect to weight change from baseline and1 months, 6 months, and 12 months; (3) compare the treatment arms with respect to immunological parameters, namely ex vivo lymphocyte proliferation; and cytokine production, namely IL-2, IL-6, INF-g INF-Alpha, IL-12, and TNF-a, and Interferon alpha at 1, 6, 12 months; and (4) correlate the above mentioned immunological markers with smear conversion rates at 1 month, 2 months, cure, relapse, and death. Finally, we suggest that this combination therapy will effectively inhibit tuberculosis infection and achieve treatment with significant effect against (TB)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) | Active comparator | Combination Product: 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB)50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 |
| 9 cis retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) | Active comparator | Combination Product: 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB)50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 9 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 |
| All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) | Active comparator | Combination Product: All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB)50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 |
| 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) | Active comparator | Combination Product: 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 |
| All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) | Active comparator | Combination Product: All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 |
| The standard therapy | Placebo comparator | Other: The standard therapyThe standard therapy 100 infected patients with confection of COVID-19 and MDR-TB will receive the standard therapy for tuberculosis for 30 days 50- 50- |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age above 18 up to 65 years
- Microbiologically or histologically confirmed active tuberculosis as well as confirmed positive with COVID-19
- Clinically confirmed latent tuberculosis
- Drug resistant MTb
- Negative pregnancy test for 18-40 year-old females
Key exclusion criteria (23 listed)
- HIV positive
- Known intolerance of vitamin D
- Sarcoidosis
- Hyperparathyroidism or nephrolithiasis
- Taking vitamin D or A supplementation in the two months preceding enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB)A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 | Combination product | 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) |
| 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB)A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 9 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 | Combination product | 9 cis retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) |
| All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB)Active Comparator: All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D 50 Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 | Combination product | All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) |
| All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized All trans retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 | Combination product | All trans retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) |
| 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB)50 Subjects with confection of COVID-19 and multidrug-resistant tuberculosis (MDR-TB) will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid in gradual 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets contain choric acid = 3.4 to 8.5 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 | Combination product | 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D For (COVID-19 and MDR-TB) |
| The standard therapyThe standard therapy 100 infected patients with confection of COVID-19 and MDR-TB will receive the standard therapy for tuberculosis for 30 days | Other | The standard therapy |
Primary outcome
Time to first negative SARS-CoV-2 PCR in NP swap and Mycobacterium tuberculosis sputum culture
Time frame: within 4 weeks
10 secondary outcomes
Sputum culture result (positive or negative)& COVID-19 PCR (positive or negative)
Time frame: 2 weeks after therapy start date
Serum levels of CRP and ESR
Time frame: one month
All cause mortality rate
Time frame: one month
Absolute lymphocyte counts (CD4,CD8 and CD25+FOXP3+ Regulatory T)
Time frame: one month
Measurement of cytokine (IFN-gamma and alpha , IL-6, IL-10, TNF-alpha, TGF-beta) levels produced in response to M. tb.
Time frame: one month
Vitamin D status
Time frame: one month
Retinoic acid status
Time frame: one month
Minocycline status
Time frame: one month
Serum indoleamine 2,3-dioxygenase (IDO) enzyme status
Time frame: one month
Chicoric Acid status
Time frame: one month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2021.
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Mahmoud R Elkazzaz, M.Sc of Biochemistry principal investigator
Faculty of Science , Damietta University
Amr K Ahmed principal investigator
Ministry of Health
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 13 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB), 9 cis retinoic acid, Minocycline, Chicroic Acid and Vitamin D for (MDR-TB) and All trans retinoic acid , Minocycline,Chicroic Acid and Vitamin D for (MDR-TB) in people with Tuberculosis, run by Kafrelsheikh University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Egypt, Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr Mahmoud R Elkazzaz, M.Sc of Biochemistry (00201090302015, mahmoudramadan2051@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first negative SARS-CoV-2 PCR in NP swap and Mycobacterium tuberculosis sputum culture (time frame: within 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2021.