Tier 2 — strong

Senolytic Drugs Attenuate Osteoarthritis-Related Articular Cartilage Degeneration: A Clinical Trial (NCT04210986)

Evans TA (Steadman Philippon Research Institute)
ClinicalTrials.gov (trial registry record with posted results — not yet published as a peer-reviewed journal article) 2024

Bibliography

Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
Steadman Philippon Research Institute.
Competing interests
Not stated in the registry record.

Study snapshot

DesignPhase I/II randomised, placebo-controlled, double-blind clinical trial in adults with knee osteoarthritis. NCT04210986.
ModelAdult human patients with knee osteoarthritis.
Sample75 actual enrollment in ClinicalTrials.gov; April 2025 OARSI abstract reports 74 randomized (34 fisetin, 40 placebo). The denominator discrepancy is unresolved; do not infer a missing arm assignment.
InterventionFisetin 100 mg capsules (approximately 20 mg/kg/day) orally for two consecutive days, then 28 days off, then repeated for two additional consecutive days — the same pulsed 'hit-and-run' schedule used in the frailty trials — versus matched placebo.
Duration12 months follow-up; primary completion January 2023, results posted September 2024.
EndpointsTreatment-emergent adverse events (primary); WOMAC knee function score; 6-minute walk distance; COMP (cartilage oligomeric matrix protein, a cartilage degradation marker); CRP (C-reactive protein); Conversion to alternative OA treatment

What the study showed, in plain terms

The Steadman Philippon Research Institute conducted a randomized placebo-controlled trial of repeated 20 mg/kg two-day fisetin courses in adults with knee osteoarthritis, with outcomes assessed for a year. ClinicalTrials.gov records 75 actual enrollment, while the separate April 2025 published OARSI meeting abstract reports 74 randomized (34 fisetin, 40 placebo). The differing denominators are not reconciled in accessible materials; both refer to one NCT04210986 trial.

No statistically significant fisetin advantage was reported for cartilage, WOMAC function and pain, walking distance or inflammatory measures at six or twelve months. The 2025 abstract also reports 185 adverse events overall, mostly minor, and four serious adverse events related to surgeries for unrelated conditions (two per arm), with no significant difference in event incidence between groups.

The results did not support clinical benefit for knee osteoarthritis at this investigational schedule. Short-term study tolerability and similar between-arm adverse-event rates do not establish safety for years of daily supplementation, different formulations or people excluded from the trial.

Key findings

  • Primary safety endpoint: no significant difference in treatment-emergent adverse events between fisetin and placebo (82% vs 83% of participants with at least one AE, p>0.9).
  • WOMAC knee function score: no significant difference at 6 months (15.2 vs 17.1, p=0.91) or 12 months (19.6 vs 15.4, p=0.44).
  • 6-minute walk distance: no significant difference at 6 months (541.8m vs 552.2m, p=0.75) or 12 months (544.2m vs 543.6m, p=0.96).
  • COMP (cartilage degradation marker): no significant difference at 6 or 12 months.
  • CRP (inflammation marker): numerically higher in the fisetin group at 6 months (32.5 vs 12.0 µg/ml), the wrong direction for benefit, though not statistically significant (p=0.083); no difference at 12 months.

What this study can and cannot tell us

  • ClinicalTrials.gov lists 75 actual enrollment, but the linked April 2025 OARSI abstract reports 74 randomized (34 fisetin and 40 placebo). The discrepancy is unresolved and should not be attributed to an unreported treatment-arm participant without source confirmation.
  • The parent registry publishes numerical outcomes and an April 2025 OARSI conference abstract summarizes additional endpoints. This is one trial with two reporting sources, not independent replications, and no full journal trial results report has been independently verified.
  • Tests one specific condition (knee osteoarthritis) and one specific dosing protocol — a null result here does not necessarily generalise to fisetin's effects on frailty, cognition, or other endpoints tested in other trials.
  • The borderline CRP signal in the unfavourable direction (p=0.083) did not reach conventional significance but is close enough to warrant mention rather than omission.
  • The sample is too small to rule out uncommon adverse events or establish safety for other doses, long-term continuous use, drug combinations, pregnancy or other excluded populations.

Related papers in the corpus

Tier 3
Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice
Zheng W et al. · International Immunopharmacology · 2017
Tier 4
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women (AFFIRM)
AFFIRM Trial et al. · ClinicalTrials.gov (trial registry record — not yet published in a peer-reviewed journal) · 2018
Tier 2
Results from a randomized clinical trial evaluating the senolytic fisetin for treating knee osteoarthritis
Scott Tashman et al. · Osteoarthritis and Cartilage · 2025

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability