Clinical trial NCT06480760: Effects of Carnosine In Patients With Peripheral Arterial Disease Patients
Official title: Effects of Carnosine In Patients With Peripheral Arterial Disease Patients; Randomized Intervention Trial (CIPHER)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Peripheral Arterial Disease
Keywords: peripheral arterial disease
carnosine
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2024-06-28
Enrollment: 144
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blinded longitudinal study in approximately 144 PAD patients
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether carnosine (a food ingredient found in chicken and red meat) supplementation (2 g) for 6 months in participants with non-claudication and claudication peripheral arterial disease (PAD) improves walking ability. Previous studies with heart failure patients have shown that carnosine supplementation increases walking capacity in these patients.

Detailed description: The objective of this double-blinded longitudinal study is to determine whether carnosine supplementation (2 g) for 6 months in participants with non-claudication and claudication peripheral arterial disease (PAD) improves walking ability. In this pilot study we will enroll 144 participants that will be divided into placebo (n=72) and carnosine groups (n=72). We will measure the distance covered on the 6-minute walk test (6-MWT) and the pain free walking capacity on the treadmill before and after the placebo or carnosine supplementation. We will measure ankle branchial index (ABI) and blood flow by magnetic resonance imaging (MRI) before and after the carnosine and placebo supplementation. In addition, we will measure carnosine by 1HMRS (Proton magnetic resonance spectroscopy), perform, global metabolomics and proteomics in the skeletal muscle, a comprehensive lipid and metabolic profile of blood, uptake of carnosine in red blood cells (RBCs), and measure carnosine aldehyde conjugates in the urine before and after 6 months of carnosine and placebo supplementation. Following completion of the study, we will follow the participants for another 3 months and examine the durability of carnosine supplementation.

Eligibility criteria: Inclusion Criteria:

1. Participants between 40-80 years of age.
2. White or African American race.
3. Literate in English.
4. ABI \>0.4-\<0.90, obtained within 6 weeks from enrollment.
5. Willing and able to comply with protocol requirements.
6. Participant is able to provide informed consent.

Exclusion Criteria:

1. As per physician's discretion, participants with HIV, hepatitis, significant liver disease, anemia, renal disease requiring dialysis, lung disease requiring home oxygen therapy, and active cancer may be excluded.
2. Critical limb ischemia with below or above the knee amputations or any form of foot ulceration over the symptomatic leg.
3. Presence of significant injury within 30 days, or vascular intervention on the symptomatic leg within 6 months before enrollment, as per physician's discretion.
4. Participants with a baseline 6MWT of less than 152.0 meters (498ft) or greater than 487.7 meters (1600ft).
5. Known allergy to L-carnosine.
6. Participants with rare autosomal recessive metabolic disorder carnosinemia or carnosinase deficiency.
7. Currently participating in other clinical trials.
8. Participation in any carnosine supplementation clinical trial anytime in the past.
9. Participants already taking carnosine.
10. Participants unable to provide urine sample (anuric).
11. Pregnant participants.
12. Participants using dual antiplatelet therapies will not be included for biopsy.
13. Participants with internal metallic objects in body will not be eligible for MRI or 1HMRS.

Primary outcomes:
measure: Measure distance covered on six-minute walk test (6MWT)
timeFrame: Baseline, 3 months, 6 months, 9 months
Secondary outcomes:
measure: Measure Ankle-Brachial Index (ABI)
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Treadmill Testing
timeFrame: Baseline, 3 months, 6 months
measure: Skin Integrity
timeFrame: Baseline, 3 months, 6 months
measure: Musculoskeletal Assessment
timeFrame: Baseline, 3 months, 6 months
measure: Neuromuscular Assessment
timeFrame: Baseline, 3 months, 6 months
measure: Balance Assessment
timeFrame: Baseline, 3 months, 6 months
measure: Quality of life Questionnaire
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Assessment of PAD Severity
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Depressive Symptoms Questionnaire
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: 24-hour Dietary Recall
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Daily Walking Ability
timeFrame: -7-Baseline, Day 90-97, Day 180-187, Day 270-277
measure: Blood Collection and Analysis
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Blood Collection and Analysis
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Measurement of Carnosine in Blood and Urine
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Measure Angiogenic Cell Population
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Mitochondrial Abundance Measurements
timeFrame: Baseline, 3 months, 6 months, 9 months
measure: Measurement of Carnosine in Muscle
timeFrame: Baseline, 6 months
measure: Measurement of Blood Flow
timeFrame: Baseline, 6 months
measure: Calf Muscle Biopsy
timeFrame: Baseline, 6 months
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville School of Medicine, Department of Medicine, Division of Environmental Medicine
state: Kentucky
city: Louisville
country: United States
facility: University Surgical Associates, 401 E. Chestnut St, Suite 710
state: Kentucky
city: Louisville
country: United States
facility: UofL Physicians - Vascular Surgery Associates, 201 Abraham Flexner Way, Suite 1004
state: Kentucky
Study officials:
affiliation: University of Louisville School of Medicine
name: Shahid Baba, PhD
role: PRINCIPAL_INVESTIGATOR
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