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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if Fisetin can reduce inflammation and frailty in elderly adults. Fisetin may help by lowering oxidative stress and improving overall health. The study focuses on older adults because they often face these health issues. Fisetin is a natural flavonoid found in many fruits and vegetables, known for its anti-inflammatory and antioxidant properties.

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.

What evidence supports the effectiveness of the drug Fisetin for treating frailty?

While there is no direct evidence for Fisetin's effectiveness in treating frailty, research suggests that dietary patterns rich in antioxidants and anti-inflammatory foods, like those found in the Mediterranean diet, may help prevent frailty. Fisetin, known for its antioxidant properties, might offer similar benefits. ^{1 2 3 4 5}

Is fisetin generally safe for human use?

Fisetin is a natural flavonoid that has been described as non-toxic and has shown various beneficial effects in studies, such as reducing inflammation and protecting nerve cells. However, specific safety data in humans is limited, and more research is needed to fully understand its safety profile. ^{6 7 8 9 10}

How is the drug fisetin unique for treating frailty?

Fisetin is unique because it is a natural compound with antioxidant and anti-inflammatory properties, which may help protect against age-related conditions like frailty by targeting multiple pathways involved in neurodegeneration and inflammation. ^{6 7 11 12 13}

Research Team

Robert Pignolo, MD, PhD

Principal Investigator

Mayo Clinic

Sundeep Khosla, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Cross-Sectional, Short-, Medium-, and Long-Term Effects of Dietary Pattern on Frailty in Taiwan. [2021]

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

Association of habitual dietary resveratrol exposure with the development of frailty in older age: the Invecchiare in Chianti study. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Nutrition and Frailty: Opportunities for Prevention and Treatment. [2022]

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

Therapeutic interventions for frail elderly patients: part II. Ongoing and unpublished randomized trials. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Healthy Eating Index to Examine Daily Food Guides Adherence and Frailty in Older Taiwanese. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

3,3',4',5,5'-Pentahydroxyflavone is a potent inhibitor of amyloid β fibril formation. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Structural requirements for the flavonoid fisetin in inhibiting fibril formation of amyloid beta protein. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Improved neuroprotective activity of Fisetin through SNEDDS in ameliorating the behavioral alterations produced in rotenone-induced Parkinson's model. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

3,3',4',5'-Tetrahydroxyflavone induces formation of large aggregates of amyloid β protein. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Preventing and Treating Neurological Disorders with the Flavonol Fisetin. [2022]

12. United States 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. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Phytomedicine-Based Potent Antioxidant, Fisetin Protects CNS-Insult LPS-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment. [2020]