Stanford School of Medicine
Cardiovascular Medicine In the Department of Medicine

New Approach for Peripheral Arterial Disease: The NO PAIN Study

Nitric Oxide for Peripheral Arterial Insufficiency

John P. Cooke, MD, PhD ( PI)
Iain Johnston, PhD
John Giacomini, MD
Andrzei Szuba, MD, PhD
Roberta K. Oka, RN, DNSc

This NIH-funded randomized clinical trial will examine the efficacy, safety and mechanisms of action of a dietary supplement, L-arginine, in patients with peripheral arterial disease. L-arginine  is a semi-essential amino acid and a component of our diet. It is  the precursor for vascular Nitric Oxide, a potent endogenous vasodilator. Studies at Stanford University, and other medical centers, suggest that dietary intake of L-arginine may be  inadequate in patients with heart or vessel disease. Dietary  supplementation with L-arginine may improve vascular nitric  oxide production. Preliminary studies have shown that L-arginine improves walking distance, angina and endothelial function.  However, no long-term trials have been conducted.

This trial will be performed in two phases. The first phase consists of a 12-week dose-response study in which we will determine the most effective dose of L-arginine in this patient population. The second phase will examine the efficacy of long-term (1-year) oral administration of L-arginine on functional status (walking ability, quality of life) and limb blood flow (plethysmography) and endothelial function (duplex ultrasonography) and angiogenesis (magnetic resonance imaging and angiography).

To be eligible for the study patients must be 18 years of age or older, have intermittent claudication or rest pain (Fontaine Class II or II) due to peripheral arterial disease, be clinically stable for at least three months, have a resting ABI < 0.9 and be able to walk at least 30 feet.

Exclusion criteria include : autoimmune disorders, nephrotic syndrome, collagen disorder, MI in the past 3 months, malabsorption syndrome, leg ulcer, gangrene; BKA; serious infection, Type I DM, uncontrolled hypertension, hepatic enzymes > 3 times normal, or creatinine >3.0, active malignancies, or planned vascular surgery or angioplasty.

Evaluation procedures will be scheduled according to participant convenience. All testing can be completed in one visit if desired at our General Clinical Research Center (GCRC) or performed in multiple visits. Once baseline evaluations are completed, patients will be randomly assigned to placebo-control oral L-arginine. All patients will be frequently monitored by telephone and asked to return to the clinic follow-up visits.

If you have patients that may be interested in participating please call:

Roberta Oka, RN, DNSc (650) 736-0504 or pager (650) 723-6661 #18106

Contact Information:


Telephone (650) 723-4064
Fax  (650) 725-1599

Postal address

Falk Cardiovascular Research Center
Stanford University Medical Center
300 Pasteur Drive
Stanford, CA 94305-5406

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