Fisetin for Frailty

(AFFIRM Trial)

Overseen By Tamara K Evans

Age: 65+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Sulfonylureas, SGLT2 inhibitors, Insulin, others

Disqualifiers: Liver disease, Renal disease, Malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to see if Fisetin, a natural substance from fruits and vegetables, can help elderly postmenopausal women with walking difficulties by reducing inflammation and protecting cells. Fisetin is a natural flavonoid found in many fruits and vegetables, known for its anti-inflammatory, antioxidant, and anti-carcinogenic properties. The goal is to improve their overall health and physical function.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications at least 2 days before and during the Fisetin treatment. This includes some antibiotics, antifungals, antivirals, and other specific drugs like statins, digoxin, and lithium. If you're on any of these, you may need to pause them temporarily.

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 confirm 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 J Pignolo, MD, PhD

Principal Investigator

Mayo Clinic

Sundeep Khosla, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for healthy postmenopausal women aged 70 or older with gait disturbances. It's not for those with significant liver/renal disease, malabsorption issues, certain hormonal disorders, recent fractures, or on medications affecting bone turnover or inducing cellular senescence.

Inclusion Criteria

I am 70 years old or older.

I am a healthy woman who has gone through menopause.

Exclusion Criteria

I have been diagnosed with hypopituitarism.

I have issues absorbing nutrients from my food.

I have problems absorbing nutrients from my food.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fisetin or placebo orally for 2 consecutive days, for 2 consecutive months

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fisetin

Trial Overview The study tests if Fisetin can reduce inflammation and improve insulin resistance, bone health, and physical function in elderly women. Participants will receive either Fisetin or a placebo to assess the potential benefits of this intervention.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Placebo capsules orally for 2 consecutive days, for 2 consecutive months.

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. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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. Japan pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. 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]

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]