Fisetin for Meniscus Tears

Overseen By Austin Stone, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Austin V Stone

Must not be taking: Losartan, Warfarin, Opioids, Senolytics

Disqualifiers: Pregnancy, Osteoarthritis, Diabetes, Depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if fisetin, a plant compound, can improve recovery after surgery for meniscus tears in the knee. Researchers are testing whether fisetin can reduce the risk of developing arthritis later by aiding knee healing. Participants will take either fisetin or a placebo (a harmless pill with no active ingredient) after surgery. The trial seeks individuals aged 18 to 45 who have had a meniscus tear repaired surgically and can walk and perform daily activities. As a Phase 2, Phase 3 trial, this study measures fisetin's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of your current medications for at least 2 months before starting the study. However, you may need to stop certain medications, such as Losartan, Warfarin, opioid analgesics, senolytic agents, and some chemotherapy drugs, among others. It's best to discuss your specific medications with the study team to see if any changes are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that fisetin, the treatment under testing, is usually well-tolerated. Earlier studies found that fisetin did not cause harmful effects in animals and is considered safe due to its anti-inflammatory properties. One study examined fisetin's effects on people with knee osteoarthritis and found it safe for humans, with no serious side effects. Overall, current evidence suggests that fisetin is a safe option for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Fisetin is unique because it targets cellular senescence, a process that contributes to tissue degeneration and inflammation, unlike traditional treatments for meniscus tears that usually focus on pain relief and physical rehabilitation. This flavonoid, found naturally in fruits and vegetables, may help promote healing by flushing out damaged cells, potentially enhancing recovery after surgery. Researchers are excited about fisetin because it offers a novel approach that could improve joint health and function more effectively than current options.

What evidence suggests that this trial's treatments could be effective for meniscus tears?

Research has shown that fisetin, a natural compound found in plants, may help manage conditions like osteoarthritis, a joint disease. Studies have discovered that fisetin targets cells that have stopped dividing, which can contribute to aging and chronic diseases. By reducing these cells, fisetin might help delay or treat joint problems, including those from meniscus injuries. Early findings suggest that fisetin could be useful in repairing or slowing down joint damage. Although more research is needed, these initial results are promising for those considering fisetin as part of their recovery from meniscus tears. Participants in this trial may receive fisetin to evaluate its effectiveness in managing meniscus tears. ^{1 6 7 8 9}

Who Is on the Research Team?

Austin Stone, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-45 who have had a surgical repair for a meniscus tear in the knee. Participants must be able to walk and follow study procedures, with stable medication use for at least 2 months before the trial. Excluded are those unable to consent or take oral meds, recent knee surgery patients, certain drug users (e.g., Warfarin), pregnant/nursing women, and individuals with severe liver/renal disease or joint diseases.

Inclusion Criteria

Subjects will be included if all the following criteria are met:

I can walk and complete physical tests.

I had surgery to repair a tear in my knee's meniscus.

Exclusion Criteria

I have received joint injections.

Subjects that have any medical condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation or prevent the patient from fully participating in all aspects of the study.

I am not taking medications that strongly affect certain liver enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the mechanobiologic intervention, including oral fisetin and real-time biofeedback, starting 8 weeks after surgery

8 weeks

Multiple visits for biofeedback sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of physical function and cartilage composition

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Fisetin
• Real-time Biofeedback Program

Trial Overview The clinical trial tests an intervention combining fisetin—a senolytic agent thought to help with cellular aging—and biofeedback after meniscal repair surgery. The goal is to improve joint loading and activity return post-surgery. Participants will either receive fisetin or a placebo capsule without knowing which one they're taking.

How Is the Trial Designed?

Group I: Fisetin Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Austin V Stone

Lead Sponsor

Trials

5

Recruited

70+

Published Research Related to This Trial

Fisetin, a natural compound found in fruits and vegetables, significantly inhibits the growth and DNA synthesis of human colon cancer cells (HT-29), with a 79% reduction in cell number observed after 72 hours at a concentration of 60 micromol/L.

The mechanism of action involves disrupting cell cycle progression, particularly causing a G(1) to S phase arrest and a G(2)/M phase block, which is linked to decreased activity of cyclin-dependent kinases (CDK) and changes in retinoblastoma protein phosphorylation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fisetin inhibits the activities of cyclin-dependent kinases leading to cell cycle arrest in HT-29 human colon cancer cells. Lu, X., Jung, Ji., Cho, HJ., et al.[2023]

Fisetin significantly reduces inflammation and oxidative stress in both an animal model (BALB/c mice) and in bovine endometrial epithelial cells (BEND) exposed to LPS, indicating its potential as a therapeutic agent against inflammatory conditions.

The protective effects of fisetin are linked to its ability to inhibit TLR4-mediated pathways and activate the Nrf2/HO-1 pathway, which together help reduce harmful reactive oxygen species (ROS) and pro-inflammatory cytokines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis. Jiang, K., Yang, J., Xue, G., et al.[2022]

Fisetin, a bioflavonoid found in fruits and vegetables, significantly reduced blood glucose and glycosylated hemoglobin levels in diabetic rats after 30 days of treatment at a dose of 10 mg/kg, while also increasing plasma insulin levels.

The study demonstrated that fisetin helps regulate carbohydrate metabolism by normalizing the activities of key enzymes in the liver and kidneys of diabetic rats, suggesting its potential as a therapeutic agent for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats. Prasath, GS., Subramanian, SP.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0047637424000952

Fisetin as a senotherapeutic agent: Evidence and ... Our review of available data suggests that targeting senescent cells with fisetin offers a promising strategy for managing multiple chronic diseases.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36243333/

The effects of fisetin on bone and cartilage: A systematic ... Fisetin, a natural flavonoid, has garnered attention as a promising pharmaceutical option for treating or delaying the progression of osteoporosis and OA.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6884076/

Meniscus repair and regeneration: A systematic review ... This review comprehensively details the current methodologies being explored in the basic sciences to stimulate better meniscus injury repair.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05088525

Meniscal Root Tears: Evaluation Using an Ultrahigh MRI Meniscal root tears have been recently recognized to be one of the most common causes for the progression of arthritis in relatively young patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05505747

Study Details | NCT05505747 | Enhancing Recovery ... The current randomized clinical trial will test a novel mechanobiologic intervention after meniscal repair that combines an oral senolytic fisetin and real-time ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05505747

Study Details | NCT05505747 | Enhancing Recovery ... The current randomized clinical trial will test a novel mechanobiologic intervention after meniscal repair that combines an oral senolytic fisetin and real-time ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04210986

NCT04210986 | Senolytic Drugs Attenuate Osteoarthritis- ... The purpose of this study is to evaluate the clinical efficacy of Fisetin (FIS), a dietary supplement, in symptomatic knee osteoarthritis (OA) patients. Key ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11806047/

First-in-human exploratory trial assessing safety, feasibility ... Meniscal tears are among the most common injuries in orthopedics. The menisci primarily function to provide joint stability and absorb shock.

9. withpower.com withpower.com/trial/phase-2-and-3-meniscus-tears-1-2023-4ab14

Fisetin for Meniscus Tears · Info for Participants Fisetin, a natural compound found in fruits and vegetables, has shown no adverse effects in animal studies and is considered safe due to its anti-inflammatory ...