Effects of Carnosine In Patients With Peripheral Arterial Disease Patients (CIPHER)

May 22, 2025 updated by: Shahid Baba

Effects of Carnosine In Patients With Peripheral Arterial Disease Patients; Randomized Intervention Trial (CIPHER)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

144

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • University of Louisville School of Medicine, Department of Medicine, Division of Environmental Medicine
        • Contact:
        • Contact:
      • Louisville, Kentucky, United States, 40202
      • Louisville, Kentucky, United States, 40202
        • Not yet recruiting
        • UofL Physicians - Vascular Surgery Associates, 201 Abraham Flexner Way, Suite 1004
        • Contact:
        • Contact:

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.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Placebo
Cellulose
Experimental: Carnosine
Carnosine 2 g daily for 6 months
Drug: Carnosine
Food ingredient (supplement)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure distance covered on six-minute walk test (6MWT)
Time Frame: Baseline, 3 months, 6 months, 9 months
Distance covered on a flat and hard surface in 6 minutes. Units: Feet
Baseline, 3 months, 6 months, 9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure Ankle-Brachial Index (ABI)
Time Frame: 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
Baseline, 3 months, 6 months, 9 months
Treadmill Testing
Time Frame: Baseline, 3 months, 6 months

Graded treadmill testing using the Gardener protocol until the onset of the maximal claudication pain.

Units: Meters
Baseline, 3 months, 6 months
Skin Integrity
Time Frame: Baseline, 3 months, 6 months
Check the color, trophic changes and flakes. Units: None
Baseline, 3 months, 6 months
Musculoskeletal Assessment
Time Frame: 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.
Baseline, 3 months, 6 months
Neuromuscular Assessment
Time Frame: Baseline, 3 months, 6 months
For neuromuscular assessment assess the sharp-dull and deep pressure sensation. Units: None
Baseline, 3 months, 6 months
Balance Assessment
Time Frame: 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
Baseline, 3 months, 6 months
Quality of life Questionnaire
Time Frame: 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.
Baseline, 3 months, 6 months, 9 months
Assessment of PAD Severity
Time Frame: 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.
Baseline, 3 months, 6 months, 9 months
Depressive Symptoms Questionnaire
Time Frame: 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.
Baseline, 3 months, 6 months, 9 months
24-hour Dietary Recall
Time Frame: 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.
Baseline, 3 months, 6 months, 9 months
Daily Walking Ability
Time Frame: -7-Baseline, Day 90-97, Day 180-187, Day 270-277
Steps over a period of 6 days using triaxial pedometer. Units: step counts
-7-Baseline, Day 90-97, Day 180-187, Day 270-277
Blood Collection and Analysis
Time Frame: 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
Baseline, 3 months, 6 months, 9 months
Blood Collection and Analysis
Time Frame: Baseline, 3 months, 6 months, 9 months
Sodium, phosphate, chloride, calcium, glucose, creatinine, albumin, ALT and AST Units: mg/dL
Baseline, 3 months, 6 months, 9 months
Measurement of Carnosine in Blood and Urine
Time Frame: Baseline, 3 months, 6 months, 9 months
Using mass spectrometry will measure carnosine bioavailability. Units: moles
Baseline, 3 months, 6 months, 9 months
Measure Angiogenic Cell Population
Time Frame: Baseline, 3 months, 6 months, 9 months
Flow cytometry: measure angiogenic cell population. Units: Number of cells
Baseline, 3 months, 6 months, 9 months
Mitochondrial Abundance Measurements
Time Frame: Baseline, 3 months, 6 months, 9 months
Perform RTPCR to measure expression of different mitochondrial genes. Units: Relative mRNA expression
Baseline, 3 months, 6 months, 9 months
Measurement of Carnosine in Muscle
Time Frame: Baseline, 6 months

Using magnetic resonance spectroscopy, will measure carnosine accumulation before and after supplementation.

Units: millimole.
Baseline, 6 months
Measurement of Blood Flow
Time Frame: Baseline, 6 months
Using magnetic resonance imaging will measure blood flow in the legs. Units: mL/min
Baseline, 6 months
Calf Muscle Biopsy
Time Frame: 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.
Baseline, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shahid Baba

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Shahid Baba, PhD, University of Louisville School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

May 20, 2025

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

June 24, 2024

First Submitted That Met QC Criteria

June 24, 2024

First Posted (Actual)

June 28, 2024

Study Record Updates

Last Update Posted (Actual)

May 29, 2025

Last Update Submitted That Met QC Criteria

May 22, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24.0309
  • R01HL163419 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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