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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Steadman Philippon Research Institute

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

Disqualifiers: Pregnancy, Liver disease, Diabetes, others

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as Losartan, Warfarin, opioid analgesics, senolytic agents, and some chemotherapy drugs. If you are taking cyclosporine, tacrolimus, repaglinide, or bosentan, you may need to stop them for at least 2 days before and during the study. Please consult with the study team for specific guidance on your medications.

What evidence supports the effectiveness of the drug Fisetin?

Research shows that Fisetin, a natural compound, has been effective in slowing the growth of various cancer cells, including oral, pancreatic, and lung cancers, by blocking certain pathways that cancer cells use to grow and spread. ^{1 2 3 4 5}

Is fisetin generally safe for humans?

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 and antioxidant properties. ^{6 7 8 9 10}

How is the drug Fisetin different from other treatments?

Fisetin is unique because it is a natural compound found in fruits and vegetables that has shown potential in treating various conditions by reducing inflammation, oxidative stress, and cancer cell growth. Unlike many conventional drugs, it targets multiple pathways involved in cell survival and apoptosis (programmed cell death), making it a promising option for cancer treatment. ^{6 10 11 12 13}

What is the purpose of this trial?

This trial tests if Fisetin, a dietary supplement, can help patients with mild to moderate knee osteoarthritis by reducing old cells that cause inflammation and cartilage breakdown.

Research Team

Thomas A Evans, MD

Principal Investigator

The Steadman Clinic

Eligibility Criteria

Inclusion Criteria

Are male or female, ages 40-80;

Are willing to comply with all study related procedures and assessments;

Are ambulatory as defined by ability to complete functional performance testing;

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fisetin or placebo for two consecutive days followed by 28 days off, repeated for a second course

2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pro-inflammatory markers, cartilage degeneration, and physical function

12 months

Long-term monitoring

Participants continue to be monitored for changes in knee function and quality of life, with assessments at 18 months

6 months

Treatment Details

Interventions

• Fisetin
• Placebo oral capsule

Participant Groups

Group I: Fisetin Experimental Treatment 1 Intervention

Fisetin 100 mg capsules (\~20 mg/ kg/ day) will be administered orally for two consecutive days (days 1 and 2) followed by 28 days off. A second course will be given for two consecutive days (days 31 and 32)

Group II: Placebo Placebo Group 1 Intervention

Placebo capsules will be administered orally for two consecutive days (days 1 and 2) followed by 28 days off. A second course will be given for two consecutive days (days 31 and 32)

Who Is Running the Clinical Trial?

Steadman Philippon Research Institute

Lead Sponsor

Trials

11

Recruited

700+

Office of Naval Research (ONR)

Collaborator

Trials

15

Recruited

660+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Fisetin-nanostructured lipid carriers (NLCs) significantly enhance the delivery and efficacy of fisetin against metastatic melanoma, showing a 3.2 times lower IC50 value and 1.8 times higher drug uptake in cancer cells compared to pure fisetin.

In vivo studies revealed that Fis-NLCs resulted in 5.9- and 10.7-fold greater inhibition of melanoma metastasis in the lungs and liver, respectively, indicating their potential as an effective treatment strategy for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma. Kumar, H., Chand, P., Pachal, S., et al.[2023]

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]

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 flavonol found in various fruits and vegetables, has demonstrated the ability to inhibit cancer cell growth in laboratory studies and in animal models, suggesting its potential as a cancer treatment.

The compound works by targeting key components of cell signaling pathways that regulate cell survival, apoptosis, and tumor growth, highlighting its multifaceted mechanism of action in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways. Rengarajan, T., Yaacob, NS.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Fisetin-loaded grape-derived nanoparticles improve anticancer efficacy in MOLT-4 cells. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-kappaB. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Exploration of Potential Targets and Mechanisms of Fisetin in the Treatment of Non-Small-Cell Lung Carcinoma via Network Pharmacology and In Vitro Validation. [2022]

6. Netherlands 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A novel 4'-brominated derivative of fisetin induces cell cycle arrest and apoptosis and inhibits EGFR/ERK1/2/STAT3 pathways in non-small-cell lung cancer without any adverse effects in mice. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Fisetin and Its Role in Chronic Diseases. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

New Propargyloxy Derivatives of Galangin, Kaempferol and Fisetin-Synthesis, Spectroscopic Analysis and In Vitro Anticancer Activity on Head and Neck Cancer Cells. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Fisetin Attenuates AKT Associated Growth Promoting Events in AflatoxinB1 Induced Hepatocellular Carcinoma. [2021]