Enhancing Recovery Through a Combined Mechanobiologic Intervention Following Meniscus Repair

NCT05505747 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 80414
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Arthroscopic meniscal procedures are the most commonly performed orthopaedic procedure in the U.S. affecting 15% of Americans ages 10-65 years. Meniscus injury is also known to increase the risk of posttraumatic osteoarthritis (PTOA). The current randomized clinical trial will test a novel intervention after meniscal repair that combines an oral senolytic fisetin and real-time biofeedback program to restore joint loading and subsequent return to activity.

Conditions

Meniscus Tear; Meniscus; Derangement; Meniscus Lesion; Meniscus Disorder

Outcome Measures

Primary Outcomes (1)

• Change in International Knee Documentation Committee (IKDC) Score between baseline and 1 year

  The IKDC Score was designed to assess patients with a variety of knee disorders including meniscal injuries. The IKDC consists of 18 items, and scores range from 0 points (lowest level of function or highest level of symptoms) to 100 points (highest level of function and lowest level of symptoms).

  Baseline, 1 year

Secondary Outcomes (1)

• Change in MRI T1rho between baseline and 1 year

  Baseline, 1 year

Study Arms (2)

Fisetin

EXPERIMENTAL

Subjects assigned to the experimental group will take approximately 20 mg/kg/day of fisetin for 2 consecutive days, followed by a 28-day senescence washout period, and then another 2-day administration. Fisetin treatment begins at 8 weeks after surgery.

Drug: Fisetin

Placebo

PLACEBO COMPARATOR

Subjects assigned to the experimental group will take approximately 20 mg/kg/day of placebo (corn starch) for 2 consecutive days, followed by a 28-day washout period, and then another 2-day administration. Placebo treatment begins at 8 weeks after surgery.

Drug: Placebo oral capsule

Interventions

Fisetin DRUG

Fisetin is a plant flavanol senolytic found in strawberries, persimmons, and cucumbers. This naturally derived senolytic has few side effects and previous animal models of both osteoarthritis and rheumatoid arthritis have demonstrated that the senolytic supplement fisetin reduces inflammation and slows cartilage breakdown.

Also known as: Novusetin, 7,3',4'-flavon-3-ol, 3,3',4',7-tetrahydroxyflavone

Fisetin

Placebo oral capsule DRUG

The oral placebo will consist of corn starch and gelatin capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects will be included if all the following criteria are met:
• Are male or female, ages 18-45;
• Are willing to comply with all study related procedures and assessments;
• Are ambulatory as defined by ability to complete functional performance testing;
• Medial, lateral or combined meniscus tear treated with surgical repair.
• Stable dose of screening/baseline medications for at least 2 months prior to the anticipated date of study drug dosing.

You may not qualify if:

• Subjects will be excluded if any of the following criteria are met:
• Females who are nursing, pregnant or planning to become pregnant during the duration of study drug dosing;
• Males who do not wish to abstain from sex or use contraceptive protection during study drug dosing and for 2 weeks after the last dose;
• Subjects who do not have the capacity to consent themselves;
• Subjects who are unable to tolerate oral medication;
• Subjects having previously undergone any of the following treatments in the stated time window.
• Surgery on the Study Knee in the past 6 months;
• Partial or complete joint replacement in the study knee. Partial or complete joint replacement in the contralateral knee is acceptable as long as the surgery was performed at least 6 months prior to enrollment and the operative knee is asymptomatic;
• Patients who have undergone arthroscopic surgery (including microfracture and meniscectomy) on the Study Knee in the last 2 years prior to the Screening visit.
• Patients will be excluded from the study if an Outerbridge grade III or IV chondral lesion is identified during arthroscopy.
• Radiographic osteoarthritis (Kellgren-Lawrence Grade 2-4), full thickness chondral defect on MRI, BMI \> 35 kg/m2, concomitant ligament injury, or prior ipsilateral knee ligament or meniscus surgery within prior 12 months of enrollment.
• The following intraarticular injections:
• Glucocorticoid within the last 2 months,
• Extended-release corticosteroid, hyaluronic acid, or other biologic injection (platelet-rich plasma, bone marrow, adipose tissue/cells) into the Study Knee in the past 6 months within the past 6 months
• Subjects with any of the following drug/medication statuses:

Sponsors & Collaborators

• Austin V Stone: lead

Study Sites (1)

UK Healthcare at Turfland

Lexington, Kentucky, 40504, United States

Location

MeSH Terms

Interventions

fisetin

Study Officials

• Austin Stone, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study pharmacist that prepared the randomization schedule will meet with the pre-specified unblinded study personnel prior to the site initiation visit. The unblinded personnel will then prepare sealed envelopes that contain each subject's group assignment. The investigators will designate, a priori, study personnel that will be unblinded. These unblinded personnel will be directly involved with maintaining the drug log and communicating with participants to schedule physical therapy sessions. The unblinded pharmacist/coordinator will access the actual treatment assignment but both blinded study personnel and the patient will not know the patient's treatment assignment. The Investigator, participant, patient assessors, laboratory personnel, and statistician will remain blinded throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: August 18, 2022
• Study Start: July 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)