Clinical Trials Logo

Clinical 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. 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),


Clinical Trial 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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05276895
Study type Interventional
Source Assiut University
Contact
Status Suspended
Phase N/A
Start date July 1, 2022
Completion date December 1, 2024

See also
  Status Clinical Trial Phase
Completed NCT04657926 - A Trial of APPA in the Treatment of Knee Osteoarthritis Phase 2
Completed NCT02536833 - A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects Phase 2
Completed NCT03014037 - Comparing Mesenchymal Stem Cell Counts in Unilateral vs. Bilateral Posterior Superior Iliac Spine Bone Marrow Aspiration N/A
Recruiting NCT05937542 - A Qualitative Investigation of CLEAT Participants
Completed NCT03644615 - A Mindfulness Program (MBSR) in the Management of Symptomatic Hip and Knee Osteoarthritis N/A
Recruiting NCT06061367 - Muscles Strength and Gait Parameteres After TKA
Withdrawn NCT04976972 - A Comparison of Patients Receiving a Total Knee Replacement With Robotic Assistance or With Conventional Instrumentation N/A
Completed NCT05496205 - A SAD Study to Evaluate the Safety, Tolerability and PK/PD of iN1011-N17 in Healthy Volunteers Phase 1
Completed NCT03850665 - Comparison of Functional Outcome in Patients After Hip Arthroplasty Depending on Surgical Approach N/A
Completed NCT02826902 - Effect of Anesthesia on Quality of Recovery in Patients Undergoing Correctional Tibial Osteotomy - A Randomized Controlled Trial N/A
Completed NCT04402502 - Dynamic 4DCT to Examine Wrist Carpal Mechanics N/A
Completed NCT02923700 - Leukocyte-rich PRP vs Leukocyte-poor PRP for the Treatment of Knee Cartilage Degeneration: a Randomized Controlled Trial Phase 4
Completed NCT04564053 - Study of Safety, Tolerability and Pharmacokinetics of LNA043 in Japanese Osteoarthritis Participants Phase 1
Completed NCT05070871 - A Clinical Trial Investigating the Effect of Salmon Bone Meal on Osteoarthritis Among Men and Women N/A
Not yet recruiting NCT05036174 - Diphenhydramine Ointment for Knee Osteoarthritis N/A
Recruiting NCT02912429 - Onlay vs. Inlay Patellofemoral Arthroplasty N/A
Recruiting NCT02666443 - Low Dose Dexamethasone in Supraclavicular Blocks N/A
Active, not recruiting NCT02723929 - Effects of tDCS and tUS on Pain Perception in OA of the Knee
Terminated NCT02820766 - Journey II BCS CMS Total Knee System Compared to Other PS Total Knee Systems in PT Setting N/A
Withdrawn NCT02921594 - Kinematic Comparison of Vanguard XP and Vanguard CR Total Knee Arthroplasties N/A