Effect of Natural Senolytic Agents & NLRP3 Inhibitors on Osteoarthritis

NCT05276895 | Suspended

• 1 other identifier: 17101628
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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),

Conditions

Osteoarthritis

Keywords

Intervention, natural senolytics, NLRP3 inhibitors, trial

Outcome Measures

Primary Outcomes (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.

  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)

• WOMAC (western Ontario and McMaster Universities Osteoarthritis Index

  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)

• IL-17

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

Study Arms (3)

(Quercetin +Fisetin)

ACTIVE COMPARATOR

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

Dietary Supplement: Quercetin and Fisetin tab.

Quercetin +Fisetin +Glycyrrhizin)

ACTIVE COMPARATOR

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 .

Dietary Supplement: Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules

Placebo

PLACEBO COMPARATOR

Placebo controlled group

Other: Placebo

Interventions

Quercetin and Fisetin tab. DIETARY_SUPPLEMENT

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

(Quercetin +Fisetin)

Quercetin Cap/Tab,Fisetin Cap/tab and Glycyrrhizin capsules DIETARY_SUPPLEMENT

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

Quercetin +Fisetin +Glycyrrhizin)

Placebo OTHER

Placebo capsule for one week every 3 weeks over 15 weeks

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University, Faculty of Medicine

Asyut, 71515, Egypt

Location

Related Publications (10)

• 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.

  PMID: 12678357 BACKGROUND

• 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.

  PMID: 28027351 BACKGROUND

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  PMID: 3101478 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis

Interventions

Quercetin; fisetin; Glycyrrhizic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Adel A. Gomaa, Ph.D.

  Assiut University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: March 14, 2022
• Study Start: July 1, 2022
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 25, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Dec.2023
• Access Criteria: Data will become available to interested investigators upon submitting a reasonable research request by email to A. Gomaa (a.gomma@aun.edu.eg).

Locations

EG (1)