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OsteoarthritisNCT05276895

Effect of Natural Senolytic Agents & NLRP3 Inhibitors on Osteoarthritis

A study testing Quercetin and Fisetin tab. and Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules in people with Osteoarthritis, run by Assiut University at 1 site in Egypt.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

Objective: To determine the efficacy of natural senolytic agents and NLRP3 Inflammasome inhibitors for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. Design: Randomized, double-blind, placebo-controlled trial. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Osteoarthritis
What is being tested?
Quercetin and Fisetin tab. and Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteEgypt
Study dates
1 Jul 2022to 1 Dec 2024
Phase
Interventional
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 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • male or female, ages 40-80;
  • Are willing to comply with all study related procedures and assessments;
  • ambulatory as defined by ability to complete functional performance testing;
  • Radiographic evidence of Kellgren-Lawrence grade II-IV osteoarthritis in one or both knees;
  • Scores 4-10 on the Numerical Rating Scale (NRS) for pain;

Who cannot join

  • Pregnant or nursing females.
  • Subjects who do not have the capacity to consent themselves.
  • Subjects who are unable to tolerate oral medication.
  • Subjects with uncontrolled medical conditions .
  • Surgery on the Study Knee in the past 6 months.
  • intra-articular injection of corticosteroids or hyaluronic acid in the past 6 months.
  • subjects with significant liver or renal disease.

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • Assiut University, Faculty of Medicine

    Asyut, 71515

Other trials in Egypt

About this study

Official title: Evaluation of the Efficacy of Natural Senolytic Agents and NLRP3 Inhibitors in Treatment of Osteoarthritis: Randomized, Double Blinded ,Placebo Controlled Trial

Objective: To determine the efficacy of natural senolytic agents and NLRP3 Inflammasome inhibitors for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis.

Design: Randomized, double-blind, placebo-controlled trial. Setting: Single-center study with outpatients from university hospital , Faculty of Medicine , Assiut, Egypt .

Participants: 60 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. Randomized to 3 arms ( natural Senolytic agents alone, natural senolytic plus natural NLRP3 Inflammasome inhibitors and placebo) Intervention: The senolytic agents act by Hit-and-run strategy therefore, intermittent dosing regimens will be applied. 1250 mg/day quercetin + 1000mg/day Fisetin for 3 consecutive days every 3 weeks (n = 20), quercetin + Fisetin for 3 consecutive days followed by 100mg/day glycyrrhizin for one week every 3 weeks (n=20) or matched placebo (n = 20) over 15 weeks Measurements: . The primary outcome measures were change in knee pain (assessed by visual analogue scale VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). Secondary outcomes are listed as follows: knee pain, function, and stiffness assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), OARSI-OMERACT (Outcome Measures in Rheumatology Clinical trials- Osteoarthritis Research Society International) responders to treatment, cartilage compositional change assessed by cartilage T2 relaxation time (ms), pain medication usage, change in quality of life (Assessment of Quality of Life (AQoL-4D) questionnaire),

Read the detailed description

Osteoarthritis is a progressive degenerative disease of the joint leading to cartilage damage, pain and loss of function affecting an estimated 250 million people worldwide and 27 million people in the United States .Currently, there are no effective FDA-approved therapies that are disease-modifying interventions to block the joint destruction pathway because of osteoarthritis. The most prevalent first-line treatment for OA is to mitigate pain and restore function with a combination of weight management, physical therapy, mind-body exercises, and analgesia with paracetamol or NSAIDs (topical or oral) . Another prominent treatment strategy is the use of intra-articular corticosteroids (CS) to reduce pain and inflammation via targeting production of interleukins, leukotrienes and prostaglandins.

However, the palliative effects of CS for OA are often short-term, can potentially lead to chondral fissuring and promotion of dose-independent structural changes in cartilage, and there are no consistent reports of efficacy .

One novel potential and appealing approach for treating osteoarthritis is through the local and systemic elimination of senescent cells. Senescent cell burden increases significantly with age and has been shown to promote several age-related pathologies including degenerative joint conditions. Senescent cells are non-proliferative, resistant to apoptosis, and secrete pro-inflammatory factors that promote disease and systemic aging .Cellular senescence can be induced by a variety of extrinsic and intrinsic signals that leads to the production of a collection of various proinflammatory cytokines and other factors that initiate senescence in neighbouring cells and promote disease and tissue dysfunction. Thus, senescent cells and their associate senescence associated secretory phenotype profiles likely play a role in both the clinical manifestation of OA (pain) and disease pathogenesis (tissue dysfunction and cartilage degradation.

The overall safety and efficacy of several senolytic drugs to treat chronic diseases have been demonstrated in several preclinical studies and more recently in phase I-II clinical trials for OA. However, there are no encouraging results with the use of natural senescent agents such as quercetin or fisetin as disease-modifying agents in OA, therefore, our study will investigate the effect of a combination of natural senescent agents and NLRP3 inhibitors on inflammation.

Inflammasomes play a crucial role in innate immunity by serving as signalling platforms which deal with a plethora of pathogenic products and cellular products associated with stress and damage. By far, the best studied and most characterized inflammasome is NLRP3 inflammasome, which consists of NLRP3 (nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3). The hyperactivation of NLRP3 inflammasome is involved in a wide range of inflammatory diseases. The search and development of anti-inflammatory drugs from natural sources of plants has received extensive attention. licorice extract has high activity and wide therapeutic effects.it has reported that glycyrrhizin could ameliorate fibrosis and inflammation via inhibiting NLRP3 inflammasome activation and NF-κB signalling pathway.

our aim is to determine the efficacy of Natural senolytic agents and NLRP3 Inflammasome inhibitors for reducing knee symptoms and effusion- synovitis in patients with symptomatic knee Osteoarthritis and knee effusion /synovitis.

Conditions
Osteoarthritis
Being tested
Quercetin and Fisetin tab., Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules, Placebo
Keywords
Intervention, natural senolytics, NLRP3 inhibitors, trial
Medical subject headings
Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Quercetin and Fisetin tab.Dietary supplement

    1250 mg/day quercetin + 1000mg/day Fisetin for 3 consecutive days every 3 weeks over 15 weeks .

  • Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsulesDietary supplement

    quercetin + Fisetin for 3 consecutive days followed by 100mg/day glycyrrhizin for one week every 3 weeks over 15 weeks

  • PlaceboOther

    Placebo capsule for one week every 3 weeks over 15 weeks

Study groups in NCT05276895
Study groupRoleWhat they receive
(Quercetin +Fisetin)Active comparator20 participants with symptomatic knee osteoarthritis and ultrasonography defined effusion-synovitis will take natural Senolytic agents. The senolytic agents act by Hit-and-run strategy therefore, intermittent dosing regimens will be applied. 1250 mg/day quercetin + 1000mg/day Fisetin for 3 consecutive days every 3 weeks.over 12 weeks
Receives: Dietary Supplement: Quercetin and Fisetin tab.
Quercetin +Fisetin +Glycyrrhizin)Active comparator20 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis will take Quercetin 1250 mg + Fisetin 1000 mg for 3 consecutive days followed by 100mg/day Glycyrrhizin for one week every 3 weeks over 12 weeks .
Receives: Dietary Supplement: Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules
PlaceboPlacebo comparatorPlacebo controlled group
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in pain on the visual analogu scale at end of treatment

    Each participant was asked to indicate his or her current level of pain on a100 mm scale.

    0 mm indcates no pain and 100mm indicates the worst pain imaginable.

    Measured: Baseline (at beginning of the trial at day 1),after 3 weeks,after 6 weeks and after 12 weeks(end of the trial)

Secondary outcomes (2)
  1. WOMAC (western Ontario and McMaster Universities Osteoarthritis Index

    For assessment of knee function, pain,and stiffness.(5 items for pain ,2 items for stiffness and 7 items for functional limitation and when score is higher means more pain and more stiffness and more functional limitation, items like using stairs ,standing from setting, walking, getting in and out of acar ,lying in bed...)

    Measured: Will be assessed before (at beginning of the trial at day 1),after 3 weeks,after 6 weeks and after 12 weeks(end of the trial)

  2. IL-17

    Laboratory test (serum sample)

    Measured: Will be measured before(at beginning of the trial )and at the end of the trial(after 12 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2022
  2. Study start1 Jul 2022
  3. Primary completion1 Sep 2024 (estimated)
  4. Study completion1 Dec 2024 (estimated)

Why it stopped: unavailability of drugs

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05276895
Sponsor's protocol ID
17101628
Status last verified
Jan 2023
First submitted
11 Jan 2022
Last updated
25 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data will become available to interested investigators upon submitting a reasonable research request by email to A. Gomaa (a.gomma@aun.edu.eg).

Publications

  • Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br. 2003 Mar;85(2):223-30. doi: 10.1302/0301-620x.85b2.13543.

    PubMed 12678357
  • da Costa BR, Hari R, Juni P. Intra-articular Corticosteroids for Osteoarthritis of the Knee. JAMA. 2016 Dec 27;316(24):2671-2672. doi: 10.1001/jama.2016.17565.

    PubMed 28027351
  • Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 Nov;27(11):1578-1589. doi: 10.1016/j.joca.2019.06.011. Epub 2019 Jul 3.

    PubMed 31278997
  • Gel'man SI. [The choice of rational modes of artificial pulmonary ventilation in cerebral operations]. Eksp Khir Anesteziol. 1965 Nov-Dec;10(6):57-60. No abstract available. Russian.

    PubMed 5873863
  • Milstein C, Clegg JB, Jarvis JM. C-terminal half of immunoglobulin lambda-chains. Nature. 1967 Apr 15;214(5085):270-2. doi: 10.1038/214270a0. No abstract available.

    PubMed 4166495
  • Stokes J, Drury RA. Gordon Roy Cameron. J Clin Pathol. 1967 Jan;20(1):5-6. doi: 10.1136/jcp.20.1.5. No abstract available.

    PubMed 5334539
  • Niemineva K. [1897--a landmark in Finnish medical literature]. Duodecim. 1966;82(17):823-7. No abstract available. Finnish.

    PubMed 5331226
  • Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002 Aug;10(2):417-26. doi: 10.1016/s1097-2765(02)00599-3.

    PubMed 12191486
  • Panich V, Sungnate T, Na-Nakorn S. Acute intravascular hemolysis and renal failure in a new glucose-6-phosphate dehydrogenase variant: G-6-PD Siriraj. J Med Assoc Thai. 1972 Dec;55(12):726-31. No abstract available.

    PubMed 4650733
  • Winniford MD, Jansen DE, Reynolds GA, Apprill P, Black WH, Hillis LD. Cigarette smoking-induced coronary vasoconstriction in atherosclerotic coronary artery disease and prevention by calcium antagonists and nitroglycerin. Am J Cardiol. 1987 Feb 1;59(4):203-7. doi: 10.1016/0002-9149(87)90785-5.

    PubMed 3101478

Questions about this trial

What is this clinical trial studying?

A study testing Quercetin and Fisetin tab. and Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules in people with Osteoarthritis, run by Assiut University at 1 site in Egypt.

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 5 inclusion and 7 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: paused, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. 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.

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?

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 from baseline in pain on the visual analogu scale at end of treatment (time frame: Baseline (at beginning of the trial at day 1),after 3 weeks,after 6 weeks and after 12 weeks(end of the trial)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05276895, which also lists 10 linked publications.

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 25 Jul 2023.

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