Fisetin to Reduce Senescence and Mobility Impairment in PAD

NCT06399809 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU00217306
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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 peripheral artery disease (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 peripheral artery disease. In exploratory analyses, the investigators will assess whether Fisetin reduces interleukin-6 (IL-6) and novel senescent markers in adipose tissue, muscle, and/or blood.

Conditions

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

Keywords

Fisetin

Outcome Measures

Primary Outcomes (1)

• Six-minute Walk Distance

  Among older people with PAD, the investigators will determine whether, compared to placebo, fisetin improves six-minute walk distance at 4-month follow-up

  Measured at baseline and 4 month follow-up

Secondary Outcomes (4)

• Hand Grip Strength

  Measured at baseline and 4 months

• Short physical performance battery (SPPB)

  Measured at baseline and 4 months

• Number of cells with senescence markers

  Measured at baseline and 4 months

• Gastrocnemius perfusion

  Measured at baseline and 4 months

Other Outcomes (7)

• Abundance of oxylipin dihomo-15d-PGJ2

  Measured at baseline and 4 months

• Abundance of interleukin-6 markers

  Measured at baseline and 4 months

• Gastrocnemius muscle fibrosis

  Measured at baseline and 4 months

Study Arms (2)

Fisetin

EXPERIMENTAL

Sharp Clinical Services will provide fisetin (100 mg capsules). Randomized participants will receive fisetin 20 mgs/kg once daily for two days, followed by 12 days without therapy. Fisetin will be dosed in 100 mg tablets. Dosing will be rounded to the nearest 100 mg. For example, a 73 kg participant with a dose of 1,460 mg (i.e.73 kg x 20 mg) receives 1,500 mgs daily (i.e. 15 x 100 mg capsules) for two days every 14 days.

Drug: Fisetin

Placebo

PLACEBO COMPARATOR

Sharp Clinical Services will provide placebo (100 mg capsules). Randomized participants will receive placebo 20 mgs/kg once daily for two days, followed by 12 days without therapy. Placebo will be dosed in 100 mg tablets. Dosing will be rounded to the nearest 100 mg. For example, a 73 kg participant with a dose of 1,460 mg (i.e.73 kg x 20 mg) receives 1,500 mgs daily (i.e. 15 x 100 mg capsules) for two days every 14 days.

Drug: Placebo

Interventions

Fisetin DRUG

Fisetin is a flavanol, present in strawberries, apples, and persimmons, that destroys senescent cells (i.e. a senolytic therapy). Of three senolytic therapies being tested in clinical trials, fisetin has the best safety profile.

Fisetin

Placebo DRUG

The placebo will be matched to the Fisetin intervention

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as:
• An ankle brachial index (ABI) less than or equal to 0.90 at baseline.
• 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.
• 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.

You may not qualify if:

• Above- or below-knee amputation
• Critical limb ischemia defined as an ABI less than 0.40 with signs or symptoms of critical limb ischemia
• Wheelchair confinement or requiring a walker to ambulate
• Walking is limited by a symptom other than PAD
• Current foot ulcer on bottom of foot
• Failure to successfully complete the study run-in
• Planned major surgery, coronary or leg revascularization during the next five months
• Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
• 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
• Mini-Mental Status Examination (MMSE) score less than 23
• Allergy to fisetin
• Currently taking fisetin or has taken fisetin in previous three months
• Non-English speaking
• Current participation in or completion of a clinical trial intervention in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a clinical trial (other than stem cell or gene therapy), participants will be eligible after the final study intervention as long as at least three months have passed since the final intervention of the trial.\]
• Visual impairment that limits walking ability.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611-3008, United States

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Peripheral Vascular Diseases; Mobility Limitation; Intermittent Claudication

Interventions

fisetin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Mary McDermott, MD

CONTACT

312-503-6419; mdm608@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a double blinded study where both the participant and the investigators collecting data will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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

Study Record Dates

• First Submitted: October 28, 2023
• First Posted: May 6, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)