Fisetin for Osteoarthritis

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Fisetin, a plant-based compound, can safely and effectively aid those with mild to moderate osteoarthritis, which causes joint pain and stiffness. Participants will receive either Fisetin or a placebo (a pill with no active ingredient) to compare results. The trial seeks individuals with knee osteoarthritis who experience regular knee pain and have not had recent knee surgeries. As a Phase 1, Phase 2 trial, this research aims to understand how Fisetin works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage treatment development.

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.

Is there any evidence suggesting that Fisetin is likely to be safe for humans?

Research shows that Fisetin, the treatment being tested in this trial, is generally safe for people. Previous studies found that Fisetin can cause mild irritation to the skin and eyes upon contact. There are no major reports of serious side effects from its use in clinical settings.

Since this trial is in the early stages, it focuses on both safety and effectiveness. Researchers are closely monitoring any side effects participants might experience. Fisetin is being tested for its potential to help with osteoarthritis, a condition affecting the joints.

Overall, while some minor irritation is possible, previous research has not identified serious safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for osteoarthritis?

Unlike the standard treatments for osteoarthritis that typically aim to relieve pain and inflammation, like NSAIDs and corticosteroids, the investigational treatment Fisetin works differently. Fisetin is a senolytic, meaning it targets and removes aged cells, which are thought to contribute to cartilage degradation in osteoarthritis. Researchers are excited because Fisetin's unique ability to clear these senescent cells could potentially slow or even reverse the progression of the disease, rather than just managing symptoms. This approach offers a novel mechanism that could change the way we treat osteoarthritis, focusing on the underlying causes rather than just the symptoms.

What evidence suggests that Fisetin might be an effective treatment for osteoarthritis?

Research shows that Fisetin, a natural substance in many fruits and vegetables, may help treat osteoarthritis. In this trial, participants will receive either Fisetin or a placebo. Studies suggest Fisetin can reduce the number of old cells that cause inflammation and tissue damage, potentially slowing cartilage damage, the smooth tissue at the ends of bones in joints. Animal studies have shown that Fisetin reduces inflammation and improves joint health. Its antioxidant properties also protect cells from damage. Although more research in humans is needed, these findings are promising for people with osteoarthritis. ^{6 7 8 9 10}

Who Is on the Research Team?

Thomas A Evans, MD

Principal Investigator

The Steadman Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fisetin
• Placebo oral capsule

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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-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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3689181/

Fisetin: A Dietary Antioxidant for Health Promotion - PMC It is reported to have neurotrophic, anticarcinogenic, anti-inflammatory, and other health beneficial effects.

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

Fisetin as a senotherapeutic agent: Evidence and ... Fisetin can reduce senescent cell numbers and attenuate pathology in animal models. •. Ongoing clinical trials are evaluating the safety and efficacy of fisetin ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05595499?cond=fisetin&aggFilters=status:&viewType=Table&rank=10

Fisetin to Improve Physical Function in Stage I-III Breast ... Giving fisetin may eliminate senescent cells and improve physical function in postmenopausal women who have received chemotherapy for breast ...

4. aging-us.com aging-us.com/article/101202/text

New agents that target senescent cells: the flavone, fisetin, ... (b-d) Fisetin is more effective in reducing viability (ATPLite) of senescent HUVECs than IMR90 cells or primary human preadipocytes. Proliferating or senescent ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9589363/

The neuroprotective effects of fisetin, a natural flavonoid in ... The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of ...

6. fishersci.com fishersci.com/store/msds?partNumber=AAL14207&productDescription=keyword&vendorId=VN00024248&countryCode=US&language=en

SAFETY DATA SHEET Precautionary Statements. Prevention. Wash face, hands and any exposed skin thoroughly after handling. Wear protective gloves/protective ...

7. assets.thermofisher.com assets.thermofisher.com/DirectWebViewer/private/results.aspx?page=NewSearch&LANGUAGE=d__EN&SUBFORMAT=d__CGV4&SKU=ALFAAL14207&PLANT=d__ALF

SAFETY DATA SHEET Precautionary Statements. Prevention. P261 - Avoid breathing dust/fume/gas/mist/vapors/spray. P264 - Wash face, hands and any exposed skin ...

8. echemi.com echemi.com/sds/smoketree-extract-pd1905101003.html

Fisetin SDS, 528-48-3 Safety Data Sheets Look through Fisetin MSDS details show. We provide Fisetin 528-48-3 safety data sheet view and download for free at Echemi.com.

9. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Fisetin

Fisetin | C15H10O6 | CID 5281614 - PubChem - NIH Primary Hazards. Irritant. Laboratory Chemical Safety Summary (LCSS) Datasheet ; Molecular Formula. C15H10O ; Synonyms. Fisetin; 528-48-3; 2-(3,4-Dihydroxyphenyl ...

10. tcichemicals.com tcichemicals.com/BE/en/sds/T2682_EU_6N.pdf

SAFETY DATA SHEET Signal word. Warning. Hazard statements. H315-Causes skin irritation. H319-Causes serious eye irritation. Precautionary statements.