Peripheral artery disease (PAD) is a common circulatory problem in which narrowed arteries reduce blood flow to your limbs, thereby restricting blood flow. During exercise or simply walking there is not sufficient blood flow to keep up with the metabolic demand. This causes symptoms, most notably leg pain when walking (intermittent claudication). PAD is also likely to be a sign of more widespread atherosclerosis which may be reducing blood flow to your heart and brain and other parts of the body, and not be isolated to just the legs. Therefore, improving blood flow to the legs in patients with PAD will likely improve blood flow to other organs as well. Reduced nitric oxide (NO) availability, or endothelial dysfunction, is a hallmark of a number of cardiovascular disorders including PAD. L-Arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. L-Arginine supplementation improves vascular reactivity and functional capacity in PAD in small, short-term studies. However, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity. As opposed to its short-term administration, long-term administration of L-arginine is not useful in patients with intermittent claudication and PAD. The objective of this application is to determine if restoring NO through an orally disintegrating tablet that releases authentic NO gas can improve blood flow and intermittent claudication in patients with PAD. The central hypothesis of this application is that a nitric oxide generating tablet can dilate blood vessels, improve blood vascular reactivity and functional capacity in patients with PAD. This same technology has already been shown to dilate blood vessels, improve vascular reactivity and functional capacity in hypertensive and pre-hypertensive patients. If successful, this non-prescription over the counter formulation can provide a safe, effective and affordable solution for patients with PAD and perhaps improve long- term outcomes in patients with vascular disorders.

Public Health Relevance

There are approximately 8 million individuals in the US with peripheral artery disease (PAD), although many are undiagnosed. Our poor record in diagnosing these individuals is in part due to insufficient education of the lay public. Insufficient nitric oxide (NO) production is a hallmark of a number of vascular disorders, including PAD. Restoring NO availability through a nitric oxide generating lozenge may have important therapeutic effects in improving blood flow and functional capacity in patients with PAD. A new therapy to improve walking distance in these individuals could improve their quality of life, reduce major adverse cardiovascular events (MACE) by permitting them to increase their physical activity.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
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Special Emphasis Panel (ZRG1-CVRS-C (10)B)
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Weber, Wendy J
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Neogenis Laboratories, Inc.
United States
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