Effects of Carnosine In Patients With Peripheral Arterial Disease Patients
- Registration Number
- NCT06480760
- Lead Sponsor
- Shahid Baba
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 144
- Participants between 40-80 years of age.
- White or African American race.
- Literate in English.
- ABI >0.4-<0.90, obtained within 6 weeks from enrollment.
- Willing and able to comply with protocol requirements.
- Participant is able to provide informed consent.
- 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.
- Critical limb ischemia with below or above the knee amputations or any form of foot ulceration over the symptomatic leg.
- Presence of significant injury within 30 days, or vascular intervention on the symptomatic leg within 6 months before enrollment, as per physician's discretion.
- Participants with a baseline 6MWT of less than 152.0 meters (498ft) or greater than 487.7 meters (1600ft).
- Known allergy to L-carnosine.
- Participants with rare autosomal recessive metabolic disorder carnosinemia or carnosinase deficiency.
- Currently participating in other clinical trials.
- Participation in any carnosine supplementation clinical trial anytime in the past.
- Participants already taking carnosine.
- Participants unable to provide urine sample (anuric).
- Pregnant participants.
- Participants using dual antiplatelet therapies will not be included for biopsy.
- Participants with internal metallic objects in body will not be eligible for MRI or 1HMRS.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Carnosine Carnosine Carnosine 2 g daily for 6 months
- Primary Outcome Measures
Name Time Method Measure distance covered on six-minute walk test (6MWT) Baseline, 3 months, 6 months, 9 months Distance covered on a flat and hard surface in 6 minutes. Units: Feet
- Secondary Outcome Measures
Name Time Method Measurement of Carnosine in Muscle Baseline, 6 months Using magnetic resonance spectroscopy, will measure carnosine accumulation before and after supplementation.
Units: millimole.Measurement of Blood Flow Baseline, 6 months Using magnetic resonance imaging will measure blood flow in the legs. Units: mL/min
Calf Muscle Biopsy Baseline, 6 months Optional muscle biopsy will be obtained by a trained vascular surgeon from the consistent location of medial gastrocnemius of the symptomatic leg using a ¼ inch bore percutaneous biopsy needle.
Measure Ankle-Brachial Index (ABI) Baseline, 3 months, 6 months, 9 months Ratio of blood pressure measurements from the arms and ankles. Units: Normal range 1.0-1.4 and lower than 0.9 is an indication of peripheral arterial disease
Treadmill Testing Baseline, 3 months, 6 months Graded treadmill testing using the Gardener protocol until the onset of the maximal claudication pain.
Units: MetersSkin Integrity Baseline, 3 months, 6 months Check the color, trophic changes and flakes. Units: None
Musculoskeletal Assessment Baseline, 3 months, 6 months Perform goniometric measurements, assess pain and conduct muscle strength testing. Upper limb muscle strength will be evaluated by hand-grip test and lower limb muscle strength will be evaluated by using a dynamometer.
Units: Visual analog scale (VAS 0-10); 0-10 corresponds to the no pain to severe pain.Neuromuscular Assessment Baseline, 3 months, 6 months For neuromuscular assessment assess the sharp-dull and deep pressure sensation. Units: None
Balance Assessment Baseline, 3 months, 6 months Balance assessment will be measured by Berg balance assessment. Units: Scale 0 to 4, with 4 indicating normal and 0 representing severe impairment
Quality of life Questionnaire Baseline, 3 months, 6 months, 9 months Health related quality of life using a Short-Form 36 general health survey. Units: An arbitrary scale 0 to 100, with higher scores representing better health.
Assessment of PAD Severity Baseline, 3 months, 6 months, 9 months To assess the leg symptoms, participants who are affirmative for the pain in legs or buttock on walking will be characterized by the responses to San Diego Claudication Questionnaire (SDCQ) and Walking Impairment Questionnaire (WIQ)
Measures: (1) intermittent claudication, (2) leg pain on exertion and rest, (3) atypical exertional leg pain, (4) atypical exertional leg pain/stop, and (5) no exertional pain.Depressive Symptoms Questionnaire Baseline, 3 months, 6 months, 9 months Depression symptoms will be evaluated using Patient Health Questionnaire-9 (PHQ-9).
Units: Scores evaluated on a 4-point scale from "not at all" to "nearly every day". PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression respectively.24-hour Dietary Recall Baseline, 3 months, 6 months, 9 months Recall of participant's dietary patterns over the past 24 hours from the time of the visit using web-based, Automated Self-Administered 24-hour (ASA24®) Dietary Assessment Tool 2024 Version.
Daily Walking Ability -7-Baseline, Day 90-97, Day 180-187, Day 270-277 Steps over a period of 6 days using triaxial pedometer. Units: step counts
Blood Collection and Analysis Baseline, 3 months, 6 months, 9 months Sodium, phosphate, chloride, calcium, glucose, creatinine, albumin, ALT and AST Units: mg/dL
Measurement of Carnosine in Blood and Urine Baseline, 3 months, 6 months, 9 months Using mass spectrometry will measure carnosine bioavailability. Units: moles
Measure Angiogenic Cell Population Baseline, 3 months, 6 months, 9 months Flow cytometry: measure angiogenic cell population. Units: Number of cells
Mitochondrial Abundance Measurements Baseline, 3 months, 6 months, 9 months Perform RTPCR to measure expression of different mitochondrial genes. Units: Relative mRNA expression
Trial Locations
- Locations (3)
University Surgical Associates, 401 E. Chestnut St, Suite 710
🇺🇸Louisville, Kentucky, United States
UofL Physicians - Vascular Surgery Associates, 201 Abraham Flexner Way, Suite 1004
🇺🇸Louisville, Kentucky, United States
University of Louisville School of Medicine, Department of Medicine, Division of Environmental Medicine
🇺🇸Louisville, Kentucky, United States