Effect of Natural Senolytic Agents & NLRP3 Inhibitors on Osteoarthritis
NCT ID: NCT05276895
Last Updated: 2023-07-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
SUSPENDED
NA
60 participants
INTERVENTIONAL
2022-07-01
2024-12-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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),
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Efficacy Evaluation of Hydrolyzed Collagen Peptide on Knees, Hips, and Ankle Pain in Osteoarthritis
NCT05369780
Home-Based Strategies for Knee Osteoarthritis
NCT07212647
The Efficacy and Safety of Curcuma Domestica Extracts and Ibuprofen in Knee Osteoarthritis
NCT00792818
Efficacy and Safety of Tongren-Dahuoluo Bolus in Patients with Knee Osteoarthritis
NCT06674759
Effects of Aquamin F on Osteoarthritis of the Knee
NCT00452101
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
(Quercetin +Fisetin)
20 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
Quercetin and Fisetin tab.
1250 mg/day quercetin + 1000mg/day Fisetin for 3 consecutive days every 3 weeks over 15 weeks .
Quercetin +Fisetin +Glycyrrhizin)
20 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 .
Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules
quercetin + Fisetin for 3 consecutive days followed by 100mg/day glycyrrhizin for one week every 3 weeks over 15 weeks
Placebo
Placebo controlled group
Placebo
Placebo capsule for one week every 3 weeks over 15 weeks
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Quercetin and Fisetin tab.
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 capsules
quercetin + Fisetin for 3 consecutive days followed by 100mg/day glycyrrhizin for one week every 3 weeks over 15 weeks
Placebo
Placebo capsule for one week every 3 weeks over 15 weeks
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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;
Exclusion Criteria
* 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.
40 Years
80 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Assiut University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Adel A.Gomaa
Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Adel A. Gomaa, Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Assiut University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Assiut University, Faculty of Medicine
Asyut, , Egypt
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
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.
Niemineva K. [1897--a landmark in Finnish medical literature]. Duodecim. 1966;82(17):823-7. No abstract available. Finnish.
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.
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.
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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
17101628
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.