RECRUITING

Fisetin to Reduce Senescence and Mobility Impairment in PAD

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-09-30

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06399809

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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.	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.

Inclusion Criteria

Exclusion Criteria

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.

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.

Contacts and Locations

Study Contact

Mary McDermott, MD

CONTACT

312-503-6419

mdm608@northwestern.edu

Study Locations (Sites)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611-3008

United States

Collaborators and Investigators

Sponsor: Northwestern University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-30

Study Completion Date2027-06

Study Record Updates

Study Start Date2024-09-30

Study Completion Date2027-06

Terms related to this study

Keywords Provided by Researchers

Fisetin

Additional Relevant MeSH Terms

Peripheral Arterial Disease
Aging
Peripheral Vascular Diseases
Walking, Difficulty
Claudication