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

STU00217306

The investigators propose a pilot randomized trial to gather preliminary data to test the hypothesis that Fisetin will reduce abundance of senescent cells in blood, skeletal muscle, and both subcutaneous and inter muscular adipose tissue and improve 6-minute walk distance in 34 people with PAD. the investigators will determine whether greater declines in abundance of cells with senescent markers are associated with greater improvement in 6-minute walk distance in people with PAD. In exploratory analyses, the investigators will assess whether Fisetin reduces SASP and novel senescent markers in adipose tissue, muscle, and/or blood.

2024-06-01

2026-11-30

2027-06-30

Not yet recruiting

Early phase I

34

Inclusion Criteria: First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as: 1. An ABI \< =0.90 at baseline. 2. Vascular lab evidence of PAD (such as a toe brachial pressure \< 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 \>0.90 and \<=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 \<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 \< 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 \<500 feet or \>1600 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 \< 7.0 g/dl, white blood count \< 2,000/mm3, white blood count \> 20,000/mm3, platelet count \< 40,000/uL. 22. eGFR\< 25 ml/min/1.73 m2 23. HemoglobinA1C \> 10 as a marker of poor diabetes control. 24. People who are 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) \>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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "To achieve the trial's specific aims, the investigators will randomize 34 participants age 50 and older with PAD to one of two groups: Fisetin vs placebo. Participants will be followed for four months", 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'This will be a double blinded study where both the participant and the investigators collecting data will be blinded.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 34, 'type': 'ESTIMATED'}}

2024-05-06