None listed
Conditions
Brief summary
Aim of Study: To determine the therapeutic efficacy and effects on arterial function of oral L-citrulline and of the combination of L-citrulline and BH4 in patients with peripheral arterial disease Background to study: Loss of the protective actions of L-arginine derived nitric oxide is a cardinal feature of endothelial dysfunction, which contributes to the pathogenesis and progression of cardiovascular disease. Supplementation with L-arginine has been shown to improve vascular function in some but not all clinical studies. Importantly L-arginine bioavailability is low. In contrast L-citrulline, a natural precursor of L-arginine, raises plasma L-arginine levels more effectively. In addition there is a naturally occurring substance called tetrahydrobipterin (BH4) which is a key co-factor in the production of nitric oxide. We believe that there may be additional benefit using the combination (L-citrulline plus BH4). Therefore this study will investigate the clinical effects of oral L-citrulline and combined BH4 supplementation in patients with peripheral arterial disease.
Interventions
Treatment regime involves 3 stages with L-citrulline, tetrahydrobiopterin (BH4) and 1 wash out period between Treatments 1 and 2. There is no wash out period between Treatments 2 and 3. Volunteers will participate in all 3 treatment stages.
Treatment 1: either L-citrulline or placebo; 3g powder in sachets taken twice a day for 12 weeks
Wash out period: 4 weeks followed by a cross-over design
Treatment 2: either L-citrulline or placebo; 3g powder in sachets taken twice a day for 12 weeks
Treatme
Treatment regime involves 3 stages with L-citrulline, tetrahydrobiopterin (BH4) and 1 wash out period between Treatments 1 and 2. There is no wash out period between Treatments 2 and 3. Volunteers will participate in all 3 treatment stages. Treatment 1: either L-citrulline or placebo; 3g powder in sachets taken twice a day for 12 weeks Wash out period: 4 weeks followed by a cross-over design Treatment 2: either L-citrulline or placebo; 3g powder in sachets taken twice a day for 12 weeks Treatment 3: all volunteers receive a combination of L-citrulline (3g powder in sachets taken twice a day) and BH4 (50mg per tablet, 3 tablets taken 3 times a day) for two weeks.
Sponsors
National Health and Medical Research Council (NHMRC)
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Male and postmenopausal women 6 months of stable intermittent claudication Peripheral artery disease (PAD) secondary to atherosclerosis Resting ankle brachial index (ABI) <0.9 and at least 25% decrease with exercise Capacity to walk more than 2 but less than 12 mins on a treadmill <25% difference in walking distance on treadmill exercise test between 2 baseline studies No change in medications or physical activity within 3 months of enrollment
Exclusion criteria
Women of child-bearing potential; Current enrollment in another clinical trial and/or ingestion of another trial agent within 30days of enrollment; Peripheral artery disease (PAD) of non-atherosclerotic nature; Fontaine class IV (4); Leg amputation above ankle; Peripheral vascular surgery, sympathectomy, angioplasty and/or stent insertion within previous 3 months; Myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery within pervious 3 months; Uncontrolled hypertension; Type I diabetes; Proliferative retinopathy; History of disease state or surgery affecting gastrointestinal absorption; Significant renal disease; Liver disease; History of treatment for any malignancy within past 5 years or evidence of active malignancy other than squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) of skin; Serious infection or hypotension associated with sepsis in previous month; Stroke within past 3 months; Autoimmune disorder; Any other acute or chronic medical condition which, in the opinion of the investigator, will increase the liklihood of the subject being unable to complete the study; Unwillingness to discontinue arginine or citrulline containing products, pentoxifylline, L-carnitine or prostacycline for at least 1 month prior to the study; Walking distance limited by conditions other than peripheral artery disease (PAD).
Outcome results
None listed