Carnosine for Peripheral Arterial Disease Patients (CAR-PAD)

July 18, 2024 updated by: Shahid Baba

Carnosine for Peripheral Arterial Disease Patients (Car-PAD)

Oral supplementation of L-carnosine will increase muscle carnosine, stabilize HIF1-alpha promote angiogenesis, and thus improve the functioning of lower extremities in PAD patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Peripheral arterial disease (PAD) is caused by atherosclerotic occlusion of the lower extremities that reduces blood flow and leads to intermittent claudication and critical limb ischemia. PAD is diagnosed by calculating the ratio of blood pressure at the ankle to that of the arm (the ankle-brachial index [ABI]). An ABI of <0.90 is indicative of atherosclerosis in the leg. Recent data from developed and developing countries have estimated that >200 million people worldwide and approximately 12 million people in United States have PAD3. Both symptomatic and asymptomatic PAD patients have an increased risk of mortality, morbidity, and a lower quality of life. With the increasing incidence of type 2 diabetes (T2D) and a rising aging population, the number of PAD patients is likely to increase. Because PAD is an under-recognized disease, currently few medications are available to improve the functional performance of these patients. Although surgical revascularization is an available treatment, grafts can fail and the stenosis can reoccur in these patients. To adequately compensate the loss of tissue due to occlusion, the current emphasis is to increase the therapeutic angiogenesis and arteriogenesis in the ischemic limb that could improve the walking ability and the quality of life in PAD patients. In a recent pre-clinical study it was shown that supplementation of carnosine(β-alanine-histidine) (500 mg/day) in heart failure patients for 6 months improves their performance on the 6-minute walking test (6MWT) compared with placebo-treated patients. Carnosine is a histidyl dipeptide present in high concentration in the skeletal muscle, brain, and heart. It is a food constituent that is present in red meat, chicken, and turkey. This dipeptide is synthesized by the ATP grasp enzyme carnosine synthetase and hydrolyzed to β-alanine and histidine by the serum and kidney carnosinase. Carnosine has the abilities to quench reactive aldehydes, bind metals, and buffer intracellular pH7. Numerous studies have shown that the supplementation of beta-alanine or carnosine increases the levels of carnosine in the skeletal muscle and improves the exercise performance in humans. Our preliminary studies with the mice model of hind limb ischemia (HLI) showed that both the pretreatment and supplementation of carnosine after femoral artery ligation increased blood flow in the ischemic limb compared with the non-treated mice. Mechanistic studies showed that the metal quenching ability of carnosine increased the expression of angiogenic factor VEGF and endothelial progenitor cells mobilization in the carnosine treated HLI mice. Similarly, the stabilization of HIF-1α, the master regulator of angiogenesis and angiogenic factor VEGF, was increased in the hypoxic C2C12 cells (murine myoblasts). Based on these pre-clinical studies, in this study PAD subjects will be recruited and supplemented with carnosine (2 g/day) for 3 months to examine if its supplementation improves walking performance compared with the baseline. Further, we will examine whether the supplementation of carnosine increases the capacity of pain-free treadmill walking time, extrusion of oxidative stress markers and mobilizes the endothelial progenitor cells in the blood.

Study Type

Interventional

Enrollment (Estimated)

20

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 Locations

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

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male subjects more than >50 to <80 years of age.
  2. White or African American race.
  3. English Speaking.
  4. ABI 0.4-< 0.60
  5. Willing to comply with protocol requirements.
  6. Able to provide informed consent. -

Exclusion Criteria:

  1. Subjects with HIV, hepatitis, significant liver disease, active infection, anemia, organ transplant, renal disease requiring dialysis, lung disease requiring oxygen, significant congenital heart disease, cancer of any type, and untreated thyroid disease.
  2. Diagnosis of carnosinemia.
  3. Known allergy to L-carnosine or meat.
  4. Presence of a pacemaker.
  5. Obesity from a known genetic defect.
  6. Dementia.
  7. Critical limb ischemia with below or above knee amputations.
  8. Foot ulcers.
  9. Major amputations.
  10. Participating in other clinical trials.
  11. End stage renal disease.
  12. Presence of significant injury within 30 days before enrollment.
  13. Prisoners.
  14. Any metallic implants.
  15. Poorly controlled diabetes (HbA1C >9%) -

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Carnosine intervention for patients with PAD
This is a single arm open labelled safety trial, where we will supplement carnosine for 3 months to subjects with non-claudication and claudication peripheral arterial disease (PAD), and determine if it improves walking ability.
Biological: Carnosine
Determine whether carnosine supplementation (2 g/day) for 3 months in peripheral arterial disease patients improves 6MWT ability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Carnosine for Peripheral Arterial Disease patients
Time Frame: One year

Compare the effects of carnosine supplementation on the 6-minute walk test (6MWT) at the baseline and after three months of carnosine supplementation.

Measure the total walking distance and compare the walking distance covered by the subjects at the start and completion of carnosine supplementation
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Graded treadmill test
Time Frame: one year
Measure the onset of claudication onset time and peak walk time
one year

Collaborators and Investigators

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

Sponsor

Shahid Baba

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)

March 1, 2023

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

April 29, 2022

First Submitted That Met QC Criteria

May 6, 2022

First Posted (Actual)

May 12, 2022

Study Record Updates

Last Update Posted (Actual)

July 22, 2024

Last Update Submitted That Met QC Criteria

July 18, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22.0098

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.

No

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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