Carnosine for Peripheral Arterial Disease

(CIPHER Trial)

Recruiting at 2 trial locations

Overseen By Shahid Baba, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shahid Baba

Must not be taking: Dual antiplatelets

Disqualifiers: HIV, Cancer, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

144 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using dual antiplatelet therapies, you will be excluded from the muscle biopsy part of the study.

What evidence supports the effectiveness of the treatment carnosine for peripheral arterial disease?

Carnosine has shown potential benefits in animal studies for improving cardiovascular risk factors due to its anti-inflammatory and antioxidant properties, but there is limited evidence in humans. Some studies suggest it may help with conditions related to diabetes and cardiovascular health, but more research is needed to confirm its effectiveness in humans. ^{1 2 3 4 5}

Is carnosine safe for humans?

Carnosine is a natural compound in the body that helps maintain balance by neutralizing harmful substances. It has been studied for its potential to protect against heart-related issues caused by air pollution, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How does the drug Carnosine differ from other treatments for peripheral arterial disease?

Carnosine is unique because it is being explored for its potential role in managing peripheral vascular disease, which is a novel approach compared to traditional treatments. Unlike other therapies that focus on correcting carnitine metabolism or improving walking performance, Carnosine may offer a different mechanism of action by potentially addressing vascular health directly. ^{6 7 9 11 12}

What is the purpose of this trial?

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.

Research Team

Shahid Baba, PhD

Principal Investigator

University of Louisville School of Medicine

Eligibility Criteria

This trial is for individuals with Peripheral Arterial Disease (PAD), which affects blood flow in the legs, causing pain or difficulty walking. Participants should be experiencing symptoms of PAD but not necessarily severe enough to prevent walking (non-claudication or claudication). Key eligibility details are not provided.

Inclusion Criteria

Willing to comply with protocol requirements

Able to provide informed consent

ABI 0.4-<0.90

Exclusion Criteria

I do not have HIV, hepatitis, significant liver disease, active infections, anemia, organ transplant, renal disease requiring dialysis, lung disease requiring oxygen, significant congenital heart disease, any type of cancer, or untreated thyroid disease.

I have been diagnosed with carnosinemia.

Presence of significant injury within 30 days before enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carnosine or placebo supplementation for 6 months to assess improvements in walking ability and other health metrics

6 months

Regular visits for assessments and measurements

Follow-up

Participants are monitored for the durability of carnosine supplementation effects

3 months

Follow-up assessments

Treatment Details

Interventions

• Carnosine

Trial Overview The study tests if taking carnosine, a dietary supplement found in chicken and red meat, can improve walking ability over six months. This follows observations that heart failure patients improved their walking capacity with carnosine.

Participant Groups

Group I: Carnosine Experimental Treatment 1 Intervention

Carnosine 2 g daily for 6 months

Group II: Placebo Active Control 1 Intervention

Cellulose

Who Is Running the Clinical Trial?

Shahid Baba

Lead Sponsor

Trials

2

Recruited

140+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a study involving 22 patients with peripheral arterial disease, L-carnitine supplementation significantly improved walking capacity in patients with low resting levels of acetylcarnitine, indicating its potential efficacy in enhancing exercise performance.

The results suggest that measuring plasma acetylcarnitine levels can help identify which patients are most likely to benefit from L-carnitine therapy, as those with elevated resting levels did not show improvement after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carnitine-related alterations in patients with intermittent claudication: indication for a focused carnitine therapy. Brevetti, G., di Lisa, F., Perna, S., et al.[2019]

In a study involving 167 cases of peripheral artery disease (PAD) and 250 matched controls, higher baseline levels of plasma amino acids like tryptophan, serine, and threonine were found to be inversely associated with the risk of developing PAD, suggesting they could serve as early biomarkers for the disease.

The Mediterranean diet supplemented with extra-virgin olive oil (EVOO) was shown to provide a protective effect against PAD, regardless of baseline threonine levels, highlighting the potential of dietary interventions in reducing PAD risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial. Razquin, C., Ruiz-Canela, M., Toledo, E., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial. [2023]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Use of carnosine in the prevention of cardiometabolic risk factors in overweight and obese individuals: study protocol for a randomised, double-blind placebo-controlled trial. [2021]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering. [2023]

5. Austria pubmed.ncbi.nlm.nih.gov

Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Carnosine as a potential therapeutic for the management of peripheral vascular disease. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Dietary intake and cardiovascular outcomes in patients with chronic vascular disease: insights from the COMPASS trial cohort. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Carnitine-related alterations in patients with intermittent claudication: indication for a focused carnitine therapy. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Protocol to assess the efficacy of carnosine supplementation in mitigating the adverse cardiovascular responses to particulate matter (PM) exposure: the Nucleophilic Defense Against PM Toxicity (NEAT) trial. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Propionyl l-carnitine: intermittent claudication and peripheral arterial disease. [2020]