{"type":"trials","record":{"id":27996,"source_id":"clinicaltrials-gov","external_id":"NCT04770064","title":"Targeting Senescence to Reduce Osteoarthritis Pain and cartilagE Breakdown (ROPE)","brief_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dosing regimens and placebo, and assess acceptability and feasibility of 2 fisetin dosing regimens.","overall_status":"Withdrawn","phases":["PHASE1","PHASE2"],"study_type":"INTERVENTIONAL","sponsor":"Austin V Stone","enrollment":0,"countries":["United States"],"start_date":"2023-06-01","completion_date":"2024-05-31","last_update_date":"2022-07-29","source_url":"https://clinicaltrials.gov/study/NCT04770064","editorial_summary":"A registered PHASE1, PHASE2 study indexed because it matched monitored longevity research terms. Registry status: Withdrawn. Registration does not establish safety or effectiveness.","first_seen_at":"2026-09-25T00:17:08.561263+00:00","last_seen_at":"2026-09-25T06:20:04.694+00:00","metadata":{"sex":"ALL","acronym":"ROPE","age_range":"35 Years to 80 Years","comparator":"Placebo","organization":"University of Kentucky","interventions":["High-dose/short-duration Fisetin","Low-dose/sustained-duration Fisetin","Oral placebo capsule"],"registry_source":"ClinicalTrials.gov","outcome_measures":["Change in markers of liver toxicity — Change between baseline and 3-month follow-up","Change in markers of kidney toxicity — Change between baseline and 3-month follow-up","Change in markers of tumor lysis syndrome — Change between baseline and 3-month follow-up","Pain Visual Analogue Scale (VAS) — Change between baseline and 3-month follow-up","Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) — Change between baseline and 3-month follow-up","Five times sit-to-stand test — Change between baseline and 3-month follow-up","Biomarker of cellular senescence (MMP-3) — Change between baseline and 3-month follow-up","Biomarker of cartilage breakdown (CTXII) — Change between baseline and 3-month follow-up"],"design_description":"RANDOMIZED · PARALLEL · TREATMENT · QUADRUPLE","source_has_results":false},"controlled_terms":["Osteoarthritis, Knee","High-dose/short-duration Fisetin","Low-dose/sustained-duration Fisetin","Oral placebo capsule"],"relevance_confidence":100,"source_quality_score":100,"freshness_score":50,"publication_state":"published","match_explanation":"Title contains controlled term: osteoarthritis.","quality_checked_at":"2026-09-25T06:20:05.499352+00:00","duplicate_cluster_key":"id:nct04770064","duplicate_of_id":null,"evidence_snapshot":{"status":"structured","version":1,"duration":"2023-06-01 to 2024-05-31","comparator":"Placebo","confidence":"structured-source","population":"ALL · 35 Years to 80 Years","provenance":{"duration":"start_date and completion_date","comparator":"registry arm fields","population":"registry eligibility fields","intervention":"registry intervention fields","participants":"enrollment","study_design":"study_type and registry design fields","evidence_stage":"phases","reported_outcome":"not available","outcomes_measured":"registry outcome-measure fields"},"generated_at":"2026-09-25T06:20:04.705Z","intervention":["High-dose/short-duration Fisetin","Low-dose/sustained-duration Fisetin","Oral placebo capsule"],"participants":0,"study_design":"RANDOMIZED · PARALLEL · TREATMENT · QUADRUPLE","subject_scope":"Human clinical study registration","evidence_stage":"PHASE1, PHASE2","safety_context":"Eligibility, adverse-event details, and clinical decisions must be checked in the official registry and with qualified clinicians.","source_support":"Structured registry protocol metadata; no finding-level conclusion is generated.","main_limitation":"This is a study registration. No reusable structured result is available here, so it cannot show whether the intervention worked or was safe.","reported_outcome":null,"outcomes_measured":["Change in markers of liver toxicity — Change between baseline and 3-month follow-up","Change in markers of kidney toxicity — Change between baseline and 3-month follow-up","Change in markers of tumor lysis syndrome — Change between baseline and 3-month follow-up","Pain Visual Analogue Scale (VAS) — Change between baseline and 3-month follow-up","Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) — Change between baseline and 3-month follow-up","Five times sit-to-stand test — Change between baseline and 3-month follow-up","Biomarker of cellular senescence (MMP-3) — Change between baseline and 3-month follow-up","Biomarker of cartilage breakdown (CTXII) — Change between baseline and 3-month follow-up"],"regulatory_context":"Trial registration is not regulatory approval and does not establish that an intervention is available."},"clinical_trial_topics":[{"topic_slug":"joint-cartilage-aging","is_published":true,"match_reasons":["Title contains controlled term: osteoarthritis.","Abstract contains controlled term: osteoarthritis.","Source terminology contains: osteoarthritis.","Title supplies longevity context: senescence.","Study type is explicitly identified as INTERVENTIONAL."],"matched_fields":["title","abstract","controlled terminology","title context","study type"],"relevance_score":100,"intelligence_topics":{"name":"Joint and cartilage ageing","slug":"joint-cartilage-aging"}}],"content_sources":{"name":"ClinicalTrials.gov","homepage_url":"https://clinicaltrials.gov/"}},"canonical_url":"https://www.immortal.life/trials/27996","automation_disclosure":"Generated automatically from cited source metadata. No scientist, clinician, researcher, editor, or human reviewer evaluates this publication before release."}