Cerebral AtherosclerosisPhase 4NCT03485495
Clinical Trial of Efficacy and Safety of Divaza for Adjustment of Oxidative Disorders in Patients With Cerebral Atherosclerosis
A Phase 4 study testing Divaza in people with Cerebral Atherosclerosis, run by Materia Medica Holding at 10 sites in Russia.
Trial summary
The purpose of this study is to obtain additional data on efficacy and safety of Divaza for adjustment of oxidative disorders in patients with cerebral atherosclerosis. It is assumed that the inclusion of the drug Divaza in the basic therapy will help reduce the severity of cognitive disorders, other clinical symptoms… Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Cerebral Atherosclerosis
- What is being tested?
- Divaza
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 10 sitesRussia
- Study dates
- 12 Apr 2018to 11 Apr 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of both genders aged 40-75 years old inclusive.
- Diagnosis of cerebral atherosclerosis verified by all three signs:
- underlying vascular disease (atherosclerosis and/or hypertension) and focal neurological symptoms combined with cerebral symptoms (headache, dizziness, tinnitus, impaired memory, working capacity);
- ultrasound signs of atherosclerotic cerebrovascular lesions (according to MAH duplex scanning within 6 months preceding the patient enrollment into the study);
- signs of morphological changes in the brain based on neuroimaging (CT/MRI 1.0-1.5 T) (subcortical and periventricular leukoaraiosis and/or focal changes in grey matter and white matter in the form of postischemic cysts and/or lacunar strokes and/or diffuse atrophic changes in the form of dilated cardiovascular system or subarachnoidal spaces).
- Cognitive disorders (MoCa <26).
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- Patients with unchanged dose and combination of basic therapy of cerebral atherosclerosis and hypertension during the previous month.
- Patients who gave their consent to use reliable contraception during the study.
- Availability of signed patient information sheet and informed consent form for participation in the clinical trial.
Who cannot join
- History of subarachnoidal/parenchymatous/ventricular hemorrhage, cerebral tumour or another disease resulting in neurological disorders.
- Ischemic-type stroke or any other acute cerebrovascular accident less than 6 months prior to the study with Modified Rankin Scale (mRs) > 1 .
- Cardiac sources of high risk or medium risk embolism (TOAST criteria).
- Signs of acute or exacerbated chronic infectious diseases at or less than 2 weeks prior to screening.
- History of CNS diseases including:
- Inflammatory CNS diseases (G00-G09)
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- Systemic Atrophies Primarily Affecting the CNS (G10-G13)
- Other degenerative diseases of the nervous system (G30-G32)
- Demyelinating diseases of the CNS (G35-G37).
- Dementia (F00-F03).
- Previously diagnosed cardiovascular diseases with functional class III or IV (according to New York Heart Association, 1964).
- Hypothyroidism, diabetes mellitus and other somatic diseases at decompensation stage.
- Uncontrollable hypertension: SBP > 180 mm Hg and/or DBP > 110 mm Hg.
- Diseases of lower limb veins (lower limb varicose veins, deep venous thrombosis, etc.) at decompensation stage.
- Any other severe concomitant pathology which, according to the investigator, may interfere with the patient's participation in the study.
- History/suspicion of oncology of any location (except for benign neoplasms).
- Allergy/intolerance of any component of the drug products used in the therapy.
- Hereditary lactose intolerance.
- Malabsorption syndrome, including congenital or acquired lactase deficiency (or any other disaccharidase deficiency) and galactosemia.
- Pregnancy, breast-feeding.
- History of treatment non-compliance, psychiatric disorders, alcoholism or drug abuse which, according to the investigator, may interfere with the study procedures.
- Use of any medicine indicated in the section "Prohibited concomitant treatment" within 1 month prior to enrollment.
- Participation in other clinical trials in the previous 3 months.
- Patients who are related to any of the on-site research personnel directly involved in the study or are an immediate relative of the study investigator, or has another conflict of interests. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted).
- Patients who work for OOO "NPF "MATERIA MEDICA HOLDING" (i.e. the company's employees, temporary contract workers, appointed officials responsible for carrying out the research or immediate relatives of the aforementioned).
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Russia10 sites
Limited Liability Company "Family policlinic no. 4"
Korolyov, 141060
Moscow City Clinical Hospital after V.M. Buyanov
Moscow, 115516
State Budgetary Institution of Healthcare of the City of Moscow City Clinical Hospital No. 1 named after. N.I. Pirogov Moscow Department of Health
Moscow, 119049
Federal State Budgetary Institution Federal Research and Clinical Center of Physical-Chemical Medicine Federal Medical Biological Agency
Moscow, 119435
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation
Moscow, 119992
Federal State Budget Scientific Institution "Scientific Center of Neurology"
Moscow, 1253678
The state budgetary health care institution of the Vladimir region "Regional Clinical Hospital"
Vladimir, 600023
Federal State Budgetary Educational Institution of Higher Education "Yaroslavl State Medical University" of the Ministry of Healthcare of the Russian Federation
Yaroslavl, 150000
State Institution of Health of the Yaroslavl Region Clinical Hospital No. 8
Yaroslavl, 150030
State budgetary institution of health care of the Yaroslavl region "Regional Clinical Hospital"
Yaroslavl, 150062
About this study
Official title: Multicenter Double-blind Placebo-controlled Randomized Parallel-group Clinical Study of Efficacy and Safety of Divaza for Adjustment of Oxidative Disorders in Patients With Cerebral Atherosclerosis
The purpose of this study is to obtain additional data on efficacy and safety of Divaza for adjustment of oxidative disorders in patients with cerebral atherosclerosis.
It is assumed that the inclusion of the drug Divaza in the basic therapy will help reduce the severity of cognitive disorders, other clinical symptoms of cerebral atherosclerosis, reduce the impact of the disease on the quality of life of the patient.
Participate in the study may be patients with a diagnosis of "cerebral atherosclerosis", which, against the backdrop of basic therapy with constant doses of drugs (within the last 4 weeks), to achieve a stable course of cerebral atherosclerosis, cognitive disorders without significant disability are detected.
Read the detailed description
Design - a multicenter randomized double-blind placebo-controlled parallel-group clinical trial.
The study will enroll the patients of either gender aged 40-75 years old inclusively with verified atherosclerotic cerebrovascular lesions (ICD-10 code - "Cerebral atherosclerosis" [I67.2]), with cognitive disorders (МоСА<26), without relevant incapacity (mRs≤1).
At screening visit (Visit 1, from day - 5 to day 0), after signing patient information sheet (informed consent form) for participation in the clinical study the patient's complaints and medical history will be collected and objective examination will be carried out. The investigator will assess intensity of cognitive disorders using MoCA, extent of functional capacity using mRs .
If the patient meets inclusion criteria and has no exclusion criteria at Visit 2 (Day 0) he/she will be randomized to one of two groups: group 1 will receive Divaza at 2 tablets 3 times a day; group 2 - placebo using study drug scheme.
Laboratory examination will be performed.
- oxidant and antioxidant systems (Fe2+-induced chemoluminescence method, ELISA) defining: 1.1. level of preformed LP products, predominantly lipid hydroperoxides; 1.2. low and very low density lipoprotein resistance to LP; 1.3. lipoprotein potential for oxidation; 1.4. serum NO product concentration (Griess reaction).
- compensatory potential of endothelium and its ability for adequate regulation of vascular tone with : 2.1. determination of platelet aggregation with bandage sign; 2.2. MAH duplex scanning. Procedures of Visit 2 may be performed on day of Visit 1 if general rules for blood collection are met, at that previously performed procedures will not be repeated.
The first administration of Divaza or Placebo will be performed at Visit 2 at medical site in the investigator's presence. The patient monitoring and therapy will last for 12 weeks during which 3 additional visits will be made.
At Visit 3 (Week 4±5 days) the investigator will collect the complaints, perform objective examination, evaluate intensity of cognitive disorders (MoCA). The investigator will monitor the prescribed, basic and concomitant therapy, evaluate therapeutic safety.
At Visit 4 (Week 8±5 days) the investigator will make a phone call to the patient to evaluate safety of the treatment.
At the final Visit 5 (Weeks 12±5 days) the investigator will evaluate intensity of cognitive disorders (MoCA). Laboratory examination of oxidant and antioxidant systems, compensatory potential of endothelium and its potential for adequate vascular tone regulation. The investigator will monitor the prescribe, basic and concomitant therapy, evaluate therapeutic safety and treatment compliance.
During the study basic, concomitant therapy will be allowed except for the products indicated in the section "Prohibited concomitant therapy".
- Conditions
- Cerebral Atherosclerosis
- Being tested
- Divaza, Placebo
- Medical subject headings
- Intracranial Arteriosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DivazaDrug
Oral administration.
PlaceboDrug
Oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Divaza | Experimental | Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved. Receives: Drug: Divaza |
| Placebo | Placebo comparator | Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean Value of Lipoprotein Resistance to LPO.
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
Measured: 12 weeks of the observation period.
Secondary outcomes (1)
Percentage of Patients With Improved Cognitive Function.
MoCA (Montreal Cognitive Assessment) score +1 and over after 12-week therapy versus baseline. Minimum score is 0, maximum score is 30. Higher values represent a better outcome.
Measured: 12 weeks of the observation period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2018
- Study start12 Apr 2018
- Primary completion11 Apr 2019
- Study completion11 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cerebral AtherosclerosisStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Materia Medica Holding
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03485495
- Sponsor's protocol ID
- MMH-DV-010
- Status last verified
- Aug 2019
- First submitted
- 26 Mar 2018
- Last updated
- 26 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Double-blind Placebo-controlled Randomized Parallel-group Clinical Study of Efficacy and Safety of Divaza for Adjustment of Oxidative Disorders in Patients With Cerebral Atherosclerosis
- ClinicalTrials.gov ID
- NCT03485495
- Acronym / sponsor ID
- MMH-DV-010
- Conditions
- Cerebral Atherosclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Materia Medica HoldingIndustry (pharma, biotech, devices)
- Study start
- 12 Apr 2018 (actual)
- Primary completion
- 11 Apr 2019 (actual)
- Study completion
- 11 Apr 2019 (actual)
- First posted
- 2 Apr 2018 (actual)
- Results
- Posted 26 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to obtain additional data on efficacy and safety of Divaza for adjustment of oxidative disorders in patients with cerebral atherosclerosis.
It is assumed that the inclusion of the drug Divaza in the basic therapy will help reduce the severity of cognitive disorders, other clinical symptoms of cerebral atherosclerosis, reduce the impact of the disease on the quality of life of the patient.
Participate in the study may be patients with a diagnosis of "cerebral atherosclerosis", which, against the backdrop of basic therapy with constant doses of drugs (within the last 4 weeks), to achieve a stable course of cerebral atherosclerosis, cognitive disorders without significant disability are detected.
Detailed description
Design - a multicenter randomized double-blind placebo-controlled parallel-group clinical trial.
The study will enroll the patients of either gender aged 40-75 years old inclusively with verified atherosclerotic cerebrovascular lesions (ICD-10 code - "Cerebral atherosclerosis" [I67.2]), with cognitive disorders (МоСА<26), without relevant incapacity (mRs≤1).
At screening visit (Visit 1, from day - 5 to day 0), after signing patient information sheet (informed consent form) for participation in the clinical study the patient's complaints and medical history will be collected and objective examination will be carried out. The investigator will assess intensity of cognitive disorders using MoCA, extent of functional capacity using mRs .
If the patient meets inclusion criteria and has no exclusion criteria at Visit 2 (Day 0) he/she will be randomized to one of two groups: group 1 will receive Divaza at 2 tablets 3 times a day; group 2 - placebo using study drug scheme.
Laboratory examination will be performed.
- oxidant and antioxidant systems (Fe2+-induced chemoluminescence method, ELISA) defining: 1.1. level of preformed LP products, predominantly lipid hydroperoxides; 1.2. low and very low density lipoprotein resistance to LP; 1.3. lipoprotein potential for oxidation; 1.4. serum NO product concentration (Griess reaction).
- compensatory potential of endothelium and its ability for adequate regulation of vascular tone with : 2.1. determination of platelet aggregation with bandage sign; 2.2. MAH duplex scanning. Procedures of Visit 2 may be performed on day of Visit 1 if general rules for blood collection are met, at that previously performed procedures will not be repeated.
The first administration of Divaza or Placebo will be performed at Visit 2 at medical site in the investigator's presence. The patient monitoring and therapy will last for 12 weeks during which 3 additional visits will be made.
At Visit 3 (Week 4±5 days) the investigator will collect the complaints, perform objective examination, evaluate intensity of cognitive disorders (MoCA). The investigator will monitor the prescribed, basic and concomitant therapy, evaluate therapeutic safety.
At Visit 4 (Week 8±5 days) the investigator will make a phone call to the patient to evaluate safety of the treatment.
At the final Visit 5 (Weeks 12±5 days) the investigator will evaluate intensity of cognitive disorders (MoCA). Laboratory examination of oxidant and antioxidant systems, compensatory potential of endothelium and its potential for adequate vascular tone regulation. The investigator will monitor the prescribe, basic and concomitant therapy, evaluate therapeutic safety and treatment compliance.
During the study basic, concomitant therapy will be allowed except for the products indicated in the section "Prohibited concomitant therapy".
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Divaza | Experimental | Drug: DivazaTablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved. |
| Placebo | Placebo comparator | Drug: PlaceboTablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients of both genders aged 40-75 years old inclusive.
- Diagnosis of cerebral atherosclerosis verified by all three signs:
- Cognitive disorders (MoCa <26).
- Patients with unchanged dose and combination of basic therapy of cerebral atherosclerosis and hypertension during the previous month.
- Patients who gave their consent to use reliable contraception during the study.
Key exclusion criteria (25 listed)
- History of subarachnoidal/parenchymatous/ventricular hemorrhage, cerebral tumour or another disease resulting in neurological disorders.
- Ischemic-type stroke or any other acute cerebrovascular accident less than 6 months prior to the study with Modified Rankin Scale (mRs) > 1 .
- Cardiac sources of high risk or medium risk embolism (TOAST criteria).
- Signs of acute or exacerbated chronic infectious diseases at or less than 2 weeks prior to screening.
- History of CNS diseases including:
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 |
|---|---|---|
| DivazaOral administration. | Drug | Divaza |
| PlaceboOral administration. | Drug | Placebo |
Primary outcome
Change in Mean Value of Lipoprotein Resistance to LPO.
Time frame: 12 weeks of the observation period.
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
1 secondary outcome
Percentage of Patients With Improved Cognitive Function.
Time frame: 12 weeks of the observation period.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Divaza in people with Cerebral Atherosclerosis, run by Materia Medica Holding at 10 sites in Russia.
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 9 inclusion and 25 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: finished, as of the sponsor's last update on 26 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Russia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mean Value of Lipoprotein Resistance to LPO. (time frame: 12 weeks of the observation period.). 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 26 Aug 2021.