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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fisetin, a natural compound, can reduce inflammation and improve mobility in elderly women with walking difficulties. Researchers aim to address age-related issues such as insulin resistance and bone weakening. Participants will receive either fisetin or a placebo to evaluate its impact on their symptoms. Women aged 70 or older who are postmenopausal and experiencing gait disturbances may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

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

Research has shown that fisetin, a natural substance in many fruits and vegetables, may help reduce inflammation and manage chronic diseases. Studies suggest it possesses anti-inflammatory and cell-protective properties and is usually well-tolerated by the body.

Although specific safety data for humans is not yet available, no negative effects have been reported from fisetin supplements. This suggests that fisetin is generally safe for people, based on current knowledge. However, since this trial is in phase 2, more information is needed to fully understand its safety, despite initial indications of safety in earlier research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for frailty, which often focus on managing symptoms with physical therapy or nutritional supplements, Fisetin offers a novel approach by targeting the biological process of aging itself. Fisetin is a natural flavonoid found in fruits like strawberries and is thought to have senolytic properties, meaning it helps clear out aging cells that contribute to frailty. Researchers are enthusiastic about Fisetin because it promises not only to slow down age-related decline but potentially improve overall health and vitality with minimal side effects. This approach could revolutionize how we think about and treat frailty, shifting from symptom management to addressing the root causes of aging.

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

Research has shown that fisetin, a natural compound found in plants, might help reduce frailty by boosting strength and lowering the risk of disability and disease. Studies have found that fisetin can target and remove old cells that contribute to aging and inflammation, potentially managing various long-term health issues. In this trial, participants will receive either fisetin or a placebo. Fisetin has been compared to medicines in its ability to maintain strength, and those taking fisetin as a supplement have reported no major side effects. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert J 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9786162/

Effects of Fisetin, a Plant-Derived Flavonoid, on Response to ... Fisetin reduced the cellular ROS levels and increased the resistance to oxidative stress. However, the response to UV irradiation was not affected by fisetin.

2. 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.

3. nad.com nad.com/news/fisetin-fights-frailty-new-study-shows-supplment-preserves-strength

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 ...

4. 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 ...

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. 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 ...

7. 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].