Fisetin for Frailty

(AFFIRM-LITE Trial)

Overseen By Tamara K Evans

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Antifungals, Antivirals, Chemotherapy, Quinolones

Disqualifiers: HIV, Hepatitis B/C, Cancer, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well a drug called Fisetin can reduce frailty and inflammation in elderly adults. Researchers aim to determine if Fisetin can lower inflammation, improve insulin resistance (how the body uses sugar), and strengthen bones. Participants will receive either Fisetin or a placebo (a pill with no active drug) for two days. This trial suits individuals aged 70 and over who do not have certain infections or take specific medications. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before and during the trial. The trial excludes participants taking specific drugs, and some medications must be paused for at least 2 days before and during the Fisetin dosing.

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

Research shows that fisetin, a natural substance in fruits and vegetables, might safely reduce inflammation and frailty. Studies have found that fisetin possesses anti-inflammatory and cell-protective properties, which could help manage several long-term diseases. Although limited safety data from human studies exist, current fisetin supplements have not been associated with harmful effects. As this study is in a mid-phase of trials, moderate evidence suggests that fisetin is generally safe for humans. However, it is important to consult a doctor before joining a trial. ^{1 2 3 4 5}

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

Researchers are excited about Fisetin for frailty because it offers a unique approach compared to traditional treatments for this condition. Unlike current options, which generally focus on managing symptoms through physical therapy and nutritional support, Fisetin is a natural compound found in fruits like strawberries, with potential anti-inflammatory and anti-aging properties. This new treatment targets cellular senescence, a process linked to aging and frailty, which is different from the mechanisms of existing therapies. The idea is that by addressing the underlying causes of frailty at the cellular level, Fisetin might improve physical function and resilience in older adults more effectively.

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

Research shows that fisetin, a natural compound found in plants, may help reduce frailty and improve strength in older adults. Studies suggest that it can remove old cells that no longer function well, potentially aiding in frailty management. Fisetin also has antioxidant properties, protecting cells from damage. Early findings indicate that it might be as effective as some medicines in maintaining physical function. Participants in this trial will receive either fisetin or a placebo to evaluate its effectiveness and safety. Although limited safety information exists for humans, no negative effects have been reported from its use in supplements. ^{2 3 6 7 8}

Who Is on the Research Team?

Robert Pignolo, MD, PhD

Principal Investigator

Mayo Clinic

Sundeep Khosla, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for people aged 70 or older who are experiencing frailty and inflammation. They must be able to take oral medication and not be on certain drugs that can't be stopped for the duration of the trial, including strong CYP3A4 inhibitors, proton pump inhibitors without a break, or senolytic agents used in the past year. Pregnant individuals, those with specific infections like hepatitis B/C or HIV, recent cancer except non-melanoma skin cancers, and those with certain lab abnormalities cannot join.

Inclusion Criteria

I am 70 years old or older.

Exclusion Criteria

I cannot or will not stop my proton pump inhibitor medication for 4 days during the Fisetin treatment.

I am not taking strong CYP3A4 inhibitors.

QTc>450 msec

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fisetin 20mg/kg/day or placebo orally for 2 consecutive days

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Fisetin

Trial Overview The study is testing Fisetin's ability to reduce signs of aging such as frailty and inflammation compared to a placebo. Participants will receive either Fisetin capsules or a placebo (a capsule with no active drug) to see if there's an improvement in their condition.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Fisetin 20mg/kg/day, orally for 2 consecutive days

Group II: Placebo Placebo Group 1 Intervention

Placebo capsules orally for 2 consecutive days

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

The self-nanoemulsifying drug delivery system (SNEDDS) significantly enhanced the effectiveness of fisetin in improving behavioral changes in rats induced by rotenone, outperforming naïve fisetin in both efficacy and bioavailability.

SNEDDS formulation not only improved the anti-Parkinsonian effects of fisetin at lower doses but also demonstrated neuroprotective properties by reducing neuronal damage, indicating a promising approach for enhancing the therapeutic potential of fisetin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved neuroprotective activity of Fisetin through SNEDDS in ameliorating the behavioral alterations produced in rotenone-induced Parkinson's model. Kumar, R., Kumar, R., Khurana, N., et al.[2022]

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]

A systematic review of the ClinicalTrials.gov registry identified various ongoing or completed trials targeting frailty in older adults, highlighting the importance of measuring frailty as a predictor of health outcomes, especially in those with cardiovascular disease.

The review covered a range of interventions, including exercise training, nutritional supplementation, and pharmaceutical agents, indicating a diverse approach to addressing frailty, although the number of published trials remains limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic interventions for frail elderly patients: part II. Ongoing and unpublished randomized trials. Bendayan, M., Bibas, L., Levi, M., et al.[2022]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6842927/

New Perspectives for Fisetin - PMC - PubMed Central - NIH Fisetin is a flavonol that shares distinct antioxidant properties with a plethora of other plant polyphenols.

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. nad.com nad.com/news/fisetin-fights-frailty-new-study-shows-supplment-preserves-strength%23:~:text=Fisetin%2520Fights%2520Frailty:%2520New%2520Study,dysfunctional)%2520cells

Fisetin Fights Frailty: New Study Shows Supplment ... Fisetin reduces vulnerability to disability and disease while improving strength. Fisetin's effectiveness is comparable to pharmaceuticals and ...

5. myagingtests.com myagingtests.com/fisetin/

Fisetin No known safety data for humans, but no reported adverse effects from supplements. There is no evidence of short or long term toxicity in mice. A mouse ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06113016

Prevention of Frailty With Fisetin and Exercise in Breast ... This phase II trial tests how well fisetin and exercise works in preventing frailty in breast cancer survivors. Fisetin is a natural substance found in ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/433176

Prevention of Frailty With Fisetin and Exercise in Breast ... This phase II trial tests how well fisetin and exercise works in preventing frailty in breast cancer survivors. Fisetin is a natural ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9961076/

Fisetin in Cancer: Attributes, Developmental Aspects, and ... They exhibit remarkable outcomes in the human body, including anti-allergic, antioxidant, anti-inflammatory, and antiviral activities [12,13].