Using Fisetin to Improve Walking in Patients with Peripheral Arterial Disease

Fisetin to Reduce Senescence and Mobility Impairment in Peripheral Artery Disease: the FIRST Pilot Randomized Trial

This study is testing if Fisetin can help people with peripheral artery disease walk better by reducing certain old cells in their bodies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Northwestern University (Academic / other)
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT06399809 on ClinicalTrials.gov

What this trial studies

This pilot randomized trial aims to evaluate the effects of Fisetin, a flavanol known for its senolytic properties, on reducing senescent cells in individuals with peripheral artery disease (PAD). The study will involve 34 participants aged 50 and older, who will be randomized to receive either Fisetin or a placebo for four months. Researchers will measure changes in the abundance of senescent cells in blood, muscle, and adipose tissue, and assess improvements in walking distance using a 6-minute walk test. Additionally, exploratory analyses will investigate the impact of Fisetin on inflammatory markers such as interleukin-6 (IL-6).

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 50 and older diagnosed with peripheral artery disease.

Not a fit: Patients with critical limb ischemia, amputations, or those whose walking limitations are due to conditions other than PAD may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved mobility and quality of life for patients with peripheral artery disease.

How similar studies have performed: While Fisetin is being tested as a senolytic therapy, this specific application in PAD is novel and has not been extensively studied.

Eligibility criteria

Inclusion Criteria:

First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as:

1. An ankle brachial index (ABI) less than or equal to 0.90 at baseline.
2. Vascular lab evidence of PAD (such as a toe brachial pressure less than or equal to 0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities.
3. An ABI of greater than 0.90 and less than or equal to 1.00 who experience a 20% or greater drop in ABI in either leg after the heel-rise test will also be included.

Exclusion Criteria:

1. Above- or below-knee amputation
2. Critical limb ischemia defined as an ABI less than 0.40 with signs or symptoms of critical limb ischemia
3. Wheelchair confinement or requiring a walker to ambulate
4. Walking is limited by a symptom other than PAD
5. Current foot ulcer on bottom of foot
6. Failure to successfully complete the study run-in
7. Planned major surgery, coronary or leg revascularization during the next five months
8. Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
9. Major medical illness including lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
10. Mini-Mental Status Examination (MMSE) score less than 23
11. Allergy to fisetin
12. Currently taking fisetin or has taken fisetin in previous three months
13. Non-English speaking
14. Current participation in or completion of a clinical trial intervention in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a clinical trial (other than stem cell or gene therapy), participants will be eligible after the final study intervention as long as at least three months have passed since the final intervention of the trial.\]
15. Visual impairment that limits walking ability.
16. Six-minute walk distance of less than 500 feet or greater than1600 feet.
17. Participation in a supervised treadmill exercise program in previous three months.
18. Participants may be excluded if they are unwilling to undergo a fat biopsy. However, if investigators find recruitment significantly slows due to this exclusion, participants may still be able to participate in the trial if they refuse the fat biopsy.
19. Women who are not menopausal will be excluded. Menopause is defined as absence of a menstrual period in the past 12 months.
20. People with a bilirubin above 2.2 mg/dl, with serum aspartate transaminase (AST) or alanine aminotransferase (ALT) more than four times the upper limit of normal.
21. Hemoglobin less than 7.0 g/dl, white blood count less than 2,000/mm3, white blood count greater than 20,000/mm3, platelet count less than 40,000/uL.
22. Estimated glomerular filtration rate (eGFR) less than 25 ml/min/1.73 m2
23. HemoglobinA1C great than 10 as a marker of poor diabetes control.
24. People who are Human Immunodeficiency Virus positive (HIV+) and people with active hepatitis B or active hepatitis C infections who do not have a low viral load.
25. People taking warfarin and other sensitive substrates of CYP2C9, CYP2C19, or CYP1A2 that have a narrow therapeutic window will be excluded, unless the drug can be held for at least two days prior to the first day of each study drug administration and can continue to be held for ten hours after the second dose of study drug administration for each of the two days of study drug dosing.
26. Body mass index (BMI) great than 43.
27. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant. In some instances, patients whose medications or laboratory data meet exclusion criteria may participate at the Principal Investigator's discretion.

Where this trial is running

Chicago, Illinois

• Northwestern University Feinberg School of Medicine — Chicago, Illinois, United States (Recruiting)

Study contacts

• Study coordinator: Mary McDermott, MD

Conditions Peripheral Arterial Disease; Aging; Peripheral Vascular Diseases; Walking, Difficulty; Claudication; Fisetin