Peripheral Arterial DiseasePhase 2FIRSTNCT06399809
Fisetin to Reduce Senescence and Mobility Impairment in PAD
A Phase 2 study testing Fisetin in people with Peripheral Arterial Disease and Aging, run by Northwestern University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Peripheral Arterial Disease, Aging, Peripheral Vascular Diseases
- What is being tested?
- Fisetin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2024to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 27Show fewer
- 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.
- Six-minute walk distance of less than 500 feet or greater than1600 feet.
- Participation in a supervised treadmill exercise program in previous three months.
- 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.
- Women who are not menopausal will be excluded. Menopause is defined as absence of a menstrual period in the past 12 months.
- 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.
- 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.
- Estimated glomerular filtration rate (eGFR) less than 25 ml/min/1.73 m2
- HemoglobinA1C great than 10 as a marker of poor diabetes control.
- 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.
- 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.
- Body mass index (BMI) great than 43.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611-3008
Kathryn J Domanchuk, 312-503-6438, k-domanchuk@northwestern.edu
Mary M. McDermott
About this study
Official title: Fisetin to Reduce Senescence and Mobility Impairment in Peripheral Artery Disease: the FIRST Pilot Randomized Trial
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.
Read the detailed description
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. Hence, 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 IL-6 and novel senescent markers in adipose tissue, muscle, and/or blood.
To achieve the trial's specific aims, 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.
- Conditions
- Peripheral Arterial Disease, Aging, Peripheral Vascular Diseases, Walking, Difficulty, Claudication
- Being tested
- Fisetin, Placebo
- Keywords
- Fisetin
- Medical subject headings
- Peripheral Arterial Disease, Peripheral Vascular Diseases, Mobility Limitation, Intermittent Claudication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FisetinDrug
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.
PlaceboDrug
The placebo will be matched to the Fisetin intervention
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured at baseline and 4 month follow-up
Secondary outcomes (4)
Hand Grip Strength
Among older people with PAD, the investigators will determine whether, compared to placebo, fisetin improves hand grip strength at 4-month follow-up.
readouts.
Measured: Measured at baseline and 4 months
Short physical performance battery (SPPB)
Among older people with PAD, the investigators will determine whether, compared to placebo, fisetin improves the short physical performance battery (SPPB) at 4-month follow-up. SPPB range, range 0-12, 12-best
Measured: Measured at baseline and 4 months
Number of cells with senescence markers
Among older people with PAD, the investigators will determine whether, compared to placebo, fisetin decreases cells with senescence markers in lower extremity adipose tissue, blood (CD3+ T lymphocytes), and gastrocnemius muscle at 4-month follow-up.
Measured: Measured at baseline and 4 months
Gastrocnemius perfusion
Among older people with PAD, the investigators will determine whether, compared to placebo, fisetin improves gastrocnemius perfusion at 4-month follow-up. The investigators will use arterial spin labeling with magnetic resonance imaging (MRI) and post-cuff occlusion hyperemia to measure changes in calf perfusion at 3 Tesla. MRI perfusion will be measured using cuff occlusion hyperemia while the participant is supine. Gastrocnemius perfusion will be measured in ml/minute per 100g of tissue.
Measured: Measured at baseline and 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start30 Sep 2024
- Primary completionNov 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mary McDermott, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06399809
- Sponsor's protocol ID
- STU00217306
- Acronym
- FIRST
- Status last verified
- Apr 2026
- First submitted
- 28 Oct 2023
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fisetin to Reduce Senescence and Mobility Impairment in Peripheral Artery Disease: the FIRST Pilot Randomized Trial
- ClinicalTrials.gov ID
- NCT06399809
- Acronym / sponsor ID
- FIRST / STU00217306
- Conditions
- Peripheral Arterial Disease, Aging, Peripheral Vascular Diseases, Walking, Difficulty, Claudication
- Keywords
- Fisetin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 6 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. Hence, 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 IL-6 and novel senescent markers in adipose tissue, muscle, and/or blood.
To achieve the trial's specific aims, 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Fisetin | Experimental | Drug: FisetinSharp 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. |
| Placebo | Placebo comparator | Drug: PlaceboSharp 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FisetinFisetin 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. | Drug | Fisetin |
| PlaceboThe placebo will be matched to the Fisetin intervention | Drug | Placebo |
Primary outcome
Six-minute Walk Distance
Time frame: Measured at baseline and 4 month follow-up
Among older people with PAD, the investigators will determine whether, compared to placebo, fisetin improves six-minute walk distance at 4-month follow-up
4 secondary outcomes
Hand Grip Strength
Time frame: Measured at baseline and 4 months
Short physical performance battery (SPPB)
Time frame: Measured at baseline and 4 months
Number of cells with senescence markers
Time frame: Measured at baseline and 4 months
Gastrocnemius perfusion
Time frame: Measured at baseline and 4 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fisetin in people with Peripheral Arterial Disease and Aging, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mary McDermott, MD (312-503-6419, mdm608@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six-minute Walk Distance (time frame: Measured at baseline and 4 month follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.