L-Citrulline in Peripheral Artery Disease

Summary

Some studies have reported improved vascular function with the supplementation of L-arginine in participants with cardiovascular disease (CVD). Several clinical studies have also begun the investigation of L-arginine supplementation in participants with peripheral artery disease (PAD). This is particularly important as currently there are limited options available to medically manage intermittent leg pain resulted from PAD. Although some of these short-term clinical trials suggested that oral L-arginine improved walking distance or improved walking speed in participants with PAD, these results were not consistent. Further, only 1% of the oral supplemented L-arginine is available for the NO production as the rest is metabolised by the body. A better way to provide the body with substrate to produce NO is therefore needed. The natural amino acid and food component, L-citrulline has been suggested to be a good candidate for this purpose.

L-citrulline, named after watermelon citrullus vulgaris from which it was first isolated, is a natural precursor of L-arginine. Studies have shown that L-citrulline is metabolised by the body to a lesser degree compared to L-arginine and hence is an effective precursor of arginine in peripheral tissues, including endothelial cells. Oral L-citrulline supplementation also eliminates some of the unwanted effects associated with oral arginine supplementation and it is well tolerated without known side effects. In addition, L-citrulline is a supplement that is available over-the-counter. Thus, oral supplementation of L-citrulline may be a new intervention strategy in participants with PAD.

The investigators hypothesize that the oral food supplement L-citrulline, unlike L-arginine, reverses endothelial dysfunction. In a multinational, multicenter, double blinded, randomised, placebo-controlled cross-over trial the effects of L-citrulline in peripheral artery disease will be investigated.

Conditions

• Peripheral Arterial Disease

Interventions

DIETARY_SUPPLEMENT

L-citrulline

L-citrulline 2 times daily 3 gram (6g/day)

DIETARY_SUPPLEMENT

Placebo

Maltodextrin 2 times daily 3 gram (6g/day)

Sponsors & Collaborators

• Clinical Trial Center Maastricht B.V.

  collaborator OTHER

• Catharina Ziekenhuis Eindhoven

  collaborator OTHER

• Hannover Medical School

  collaborator OTHER

• Maastricht University

  lead OTHER

Principal Investigators

• Harald Schmidt, Prof. · Maastricht University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-08-01

Primary Completion

2019-02-20

Completion

2019-08-30

Countries

• Germany
• Netherlands

Study Locations