The Effects of Oral Inorganic Nitrate Supplementation on Lower Limb Perfusion During Exercise in Patients With PAD

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Peripheral arterial disease (PAD) is a highly prevalent and costly condition. Intermittent claudication (IC), defined as ischemic leg pain that occurs with walking, results in functional impairment, reduced daily physical activity, and a lower quality of life. Although the mechanisms contributing to functional impairment are not fully delineated, current evidence suggests that the uncoupling of skeletal muscle cellular metabolism from tissue perfusion may be responsible for exercise intolerance. We have previously shown increases in plasma inorganic nitrite, via oral nitrate, produced clinically significant increases exercise performance in patients with PAD+IC.

The hypothesis of this proposal is in patients with PAD+IC, 3-6 days of oral dietary nitrate consumption (in the form of concentrated beetroot juice) will produce a greater tissue perfusion, oxygen delivery, and enhanced muscle metabolism in comparison to placebo. This will translate into an increase in physical performance in both muscle specific plantar flexion exercise and treadmill measures of pain free ambulation. In order to test this hypothesis, we will recruit 10 patients PAD+IC in a randomized, double-blind, placebo controlled, cross over design.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Virginia

Criteria

Inclusion Criteria:

• - History of stable intermittent claudication for 3 or more months, and an Ankle-brachial index test (ABI) <0.9 at rest.

• Symptomatic PAD (claudication or critical limb ischemia)

Exclusion Criteria:

• - Limb threatening ischemia, including rest pain and/or gangrene; impending limb loss or chronic osteomyelitis.

• Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months of enrollment;

• severe peripheral neuropathy or any condition other than PAD that limits walking such as unstable angina;

• history of significant left main or three vessel coronary artery disease (>70% stenosis, unprotected by grafts) or recent myocardial infarction (6 weeks);

• chest pain during treadmill exercise which appears before the onset of claudication,

• chronic renal failure with an eGRF<30; Type 1diabetes mellitus, a BMI>40, and a HbA1c>8.5%. Refusal to give or inability to give informed consent. Pregnancy (Self-reported).