The Impact of Branched-Chain Amino Acid Metabolism on Limb Dysfunction in PAD

NCT ID: NCT03490968

Last Updated: 2024-02-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-22
• Study Completion Date: 2023-08-22

Brief Summary

Test the theory that abnormalities in the large blood vessels that deliver blood to your leg and the very small blood vessels in your leg's muscles (invisible to the eye) work together to worsen your leg function and walking.

Conditions

Peripheral Arterial Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Healthy Subjects

Group Type: OTHER

Vascular Assessment

Intervention Type: BEHAVIORAL

Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age.

Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy.

Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.

Peripheral Artery Disease (PAD) with Supervised Exercise

Subjects will be referred for supervised exercise therapy. Subjects will have 3 visits per week for 12 weeks. Each visit will include a minimum of 30 to 40 minutes of exercise to improve ambulation with a certified trainer.

Group Type: EXPERIMENTAL

Supervised Exercise

Intervention Type: BEHAVIORAL

Subjects will have 3 visits per week for 12 weeks.

Vascular Assessment

Intervention Type: BEHAVIORAL

Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age.

Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy.

Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.

PAD Subjects Who Undergo Revascularization of the Leg

This group of subjects are receiving leg revascularization as part of standard of care.

Group Type: ACTIVE_COMPARATOR

Vascular Assessment

Intervention Type: BEHAVIORAL

Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age.

Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy.

Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.

Interventions

Supervised Exercise

Subjects will have 3 visits per week for 12 weeks.

Intervention Type: BEHAVIORAL

Vascular Assessment

Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age.

Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy.

Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Male or female, age ≥ 50 years old
• Non-smoker

• Male or female, age 50 years or older
• Atherosclerotic PAD, ABI ≤0.85
• Willing to comply with protocol, attend follow-up appointments, complete all study assessments, and provide informed consent
• For Aim 3, subjects will have Rutherford stage 4 or 5 disease
• For Aim 3, subjects will be undergoing revascularization as standard of care

Exclusion Criteria

• Presence of peripheral artery disease
• History of a heart attack or stroke
• Diabetes
• Active cancer
• Severe renal disease (CrCl < 60)
• Severe liver disease
• Active rheumatological diseases

• Presence of a femoral, popliteal or tibial aneurysm of the index limb
• Life expectancy less than 2 years
• A vascular disease prognosis that includes an anticipated above ankle amputation on index limb within 4 weeks of index procedure
• Renal dysfunction defined as MDRD eGFR ≤ 20ml/min/173 m2 at the time of screening
• Currently on dialysis or history of a renal transplant
• Cirrhosis or active hepatitis
• A documented hypercoagulable state
• Myocardial infarction within 6 months
• Stroke within 6 months
• Nonatherosclerotic occlusive disease of the lower extremity
• Any prior infrainguinal revascularization on index limb
• Current immunosuppressive medication, chemotherapy or radiation therapy
• Inability to have an MRI
• Exercise limitation aside from that due to PAD (i.e. COPD, degenerative joint disease, etc.)
• Women who are pregnant
• Women who are nursing
• Primary indications for systemic oral anticoagulation for active arterial or venous thromboembolic disease.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joshua Beckman

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua Beckman, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

Sullivan AE, Behroozian A, Coolbaugh C, Shardelow E, Smith EK, Wells QS, Clair DG, Aday AW, Garrard CL 3rd, Curci JA, Holder TA, Barnett JV, Freiberg MS, Crescenzi RL, Wakeham DJ, Hearon CM Jr, Donahue MJ, Beckman JA. Microvascular Function and Ambulatory Capacity in Peripheral Artery Disease. Circ Cardiovasc Interv. 2025 Sep 4:e015582. doi: 10.1161/CIRCINTERVENTIONS.125.015582. Online ahead of print.

Reference Type: DERIVED

PMID: 40905129 (View on PubMed)

Other Identifiers

18SFRN33900069

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

180441

Identifier Type: -

Identifier Source: org_study_id