NCT04770064

Targeting Senescence to Reduce Osteoarthritis Pain and cartilagE Breakdown (ROPE)

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Austin V Stone · Academic / Other
• Sex: All
• Age: 35 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Symptomatic knee osteoarthritis (OA) is the most common joint disorder in the U.S. and a leading cause of disability. Increasing age, obesity, and previous injury increase the lifetime risk of knee OA, but these factors are also independently associated with increased cellular senescence. Senescent cells accumulate in many tissues and contribute to chronic pathologies, linked to the secretion of pro-inflammatory factors collectively known as the senescence-associated secretory phenotype. In OA, senescent cells promote production of cytokines, chemokines, and matrix-degrading enzymes involved in progressive cartilage breakdown. The senolytic supplement fisetin alters the inflammatory and catabolic cartilage responses, which may clinically lessen OA pain while also slowing progressive cartilage breakdown. The purpose of this double-blind, randomized clinical trial is to compare 2 fisetin dosing regimens versus placebo. Sixty patients with mild to moderate knee OA will be assessed at baseline and 3 months in an effort to: determine if 2 different fisetin dosing regimens lessen pain and functional impairment compared to placebo, compare progressive changes in senescent cell activity and biomarkers of cartilage degradation between different fisetin dosing regimens and placebo, and assess acceptability and feasibility of 2 fisetin dosing regimens.

Conditions

• Osteoarthritis, Knee

Interventions

Type	Name	Description
DRUG	High-dose/short-duration Fisetin	Fisetin is a plant flavanol senolytic found in strawberries, persimmons, and cucumbers. It has senolytic properties that may provide therapeutic benefit for those with knee osteoarthritis. Participants will be asked to take approximately 20 mg/kg of body mass for 2 consecutive days, followed by a 28-day washout period, and then another 2-day administration.
DRUG	Low-dose/sustained-duration Fisetin	Fisetin is a plant flavanol senolytic found in strawberries, persimmons, and cucumbers. It has senolytic properties that may provide therapeutic benefit for those with knee osteoarthritis. Participants will be asked to take one, 100 mg capsule of fisetin daily for 90 days.
OTHER	Oral placebo capsule	Participants will be asked to take one, 100 mg oral placebo capsule (corn starch) daily for 90 days.

Timeline

• Start date: 2023-06-01
• Primary completion: 2024-05-31
• Completion: 2024-05-31
• First posted: 2021-02-25
• Last updated: 2022-07-29

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study