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L-Arginine in the Treatment of Peripheral Arterial Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00284076
First Posted: January 31, 2006
Last Update Posted: March 5, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
Stanford University
  Purpose
To assess the effects of L-arginine upon functional status (treadmill exercise testing; quality of life) and limb blood (by mercury strain gauge plethysmography) in peripheral arterial disease.

Condition Intervention
Cardiovascular Diseases Peripheral Vascular Diseases Drug: L-arginine

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Stanford University:

Study Start Date: February 2000
Study Completion Date: July 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

Peripheral arterial disease is a common disorder effecting up to 15% of men over age 55 and women over age 65. Patients with peripheral arterial disease are at increased risk for stroke, myocardial infarction or other adverse vascular outcomes. Therapy for this disorder is currently limited with only 2 FDA approved drugs (Pentoxifylline, cilostazol). These agents improve walking distance by 10 to 40 percent. Other agents such as verapamil and prostacyclin analogs have significant side effects. Although therapy with angiogenesis inducers, including injections of plasmid constructs for vascular endothelial growth factor (VEGF) or VEGF protein, is beneficial, the widespread applicability of this therapy is questionable. The study used an alternative approach, which may be safer and more effective. The basis for this approach is the ability of L-arginine to enhance endogenous vascular nitric oxide production, improving blood flow acutely. Furthermore, since several angiogenic growth factors may act at least partially through the production of nitric oxide, this therapy could produce a sustained benefit by the induction of an increase in skeletal muscle capillary density.

DESIGN NARRATIVE:

A randomized placebo-controlled trial to assess the effects of L-arginine on functional status was performed in patients with peripheral arterial disease. Blood flow was assessed by Doppler and plethysmography and measures of nitric oxide synthesis (plasma and urinary nitrogen oxides) were performed. The effect of L-arginine on treadmill walking distance was determined. The potential for L-arginine induced angiogenesis was assessed using magnetic resonance angiography.

There were two separate studies of oral L-arginine. The first was a dose ranging study involving 80 patients receiving four different doses of L-arginine (9 grams, 6 grams, 3 grams, or 0 grams). The dosing of L-arginine was performed in a randomized placebo-controlled fashion. Patients receive six weeks of therapy. Patients with diabetic retinopathy, active malignancy or previous malignancy in a state of remission, or autoimmune disorders were excluded. Ophthalmological exams were performed to screen for pathological angiogenesis in the retina. After the completion of the dose response study, the investigators studied the safety and efficacy of prolonged (12 months) L-arginine therapy. The primary end point was absolute claudication distance (ACD) and a statistical analysis was performed of the logarithm ACDT / ACDB. A treadmill was performed at one month after cessation of therapy to determine if there was a structural alteration of the indices of limb hemodynamics including the ankle brachial index (ABI) and plethysmography was performed at 6 and 12 months of therapy and at 1 month after sensation of therapy. The study correlated measures of limb blood flow with evidence of increased nitric oxide synthesis by measuring urinary nitrogen oxide. Flow mediated vasodilation (FMVD) of the brachial artery was measured. The choice of monitoring flow mediated vasodilation of the brachial artery, while appropriate for showing a systemic enhancement of nitric oxide synthesis, would not directly support an improvement of endothelial function in the vascular bed of interest.

Asymmetric dimethylarginine (ADMA) was measured with the prediction that patients with elevated ADMA levels, depressed urinary nitrogen oxides and reduced FMVD might be more responsive to L-arginine therapy. A second aim of the protocol was to determine if the chronic enhancement of nitric oxide synthesis by L-arginine supplementation had an enduring effect on conduit vessel structure. The ankle brachial index, plethysmography, and MR perfusion imaging were performed at 0, 6 and 12 months on therapy, and at 1 month after cessation of therapy.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
Patients with diabetic retinopathy, active malignancy or previous malignancy in a state of remission, or autoimmune disorders will be excluded.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00284076


Sponsors and Collaborators
Stanford University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
OverallOfficial: John Cooke Stanford University
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00284076     History of Changes
Other Study ID Numbers: 357
T32HL007708 ( U.S. NIH Grant/Contract )
P50HL083800 ( U.S. NIH Grant/Contract )
P01AI050153 ( U.S. NIH Grant/Contract )
R01HL075774 ( U.S. NIH Grant/Contract )
R01HL063685 ( U.S. NIH Grant/Contract )
First Submitted: January 27, 2006
First Posted: January 31, 2006
Last Update Posted: March 5, 2014
Last Verified: March 2014

Additional relevant MeSH terms:
Cardiovascular Diseases
Vascular Diseases
Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases