Peripheral Arterial Disease
Conditions
Keywords
peripheral arterial disease, carnosine
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.
Interventions
DRUGCarnosine
Food ingredient (supplement)
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Shahid Baba
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
A randomized, double-blinded longitudinal study in approximately 144 PAD patients
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Treadmill Testing | Baseline, 3 months, 6 months | Graded treadmill testing using the Gardener protocol until the onset of the maximal claudication pain. Units: Meters |
| Skin 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. |
| 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 |
| 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 | White blood cells, red blood cells. Units: Cells per cubic millimeter. Neutrophils, lymphocytes, monocytes, eosinophils, basophils. Units: percent |
| 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 |
| 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. |
| 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. |
Countries
United States
Contacts
Primary ContactShahid Baba, PhD
Backup ContactAmit Dwivedi, MD
Outcome results
None listed