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

Description

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.

Conditions

Peripheral Arterial Disease, Peripheral Vascular Diseases

Study Overview

Study Details

Study overview

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.

The Effects of Oral Inorganic Nitrate Supplementation on Lower Limb Perfusion and Metabolism During Exercise in Patients With Peripheral Arterial Disease (PAD)

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

Condition
Peripheral Arterial Disease
Intervention / Treatment

-

Contacts and Locations

Charlottesville

University of Virginia, Charlottesville, Virginia, United States, 22903

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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)
  • * - 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).

Ages Eligible for Study

40 Years to 80 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Virginia,

Jason D. Allen, PhD, PRINCIPAL_INVESTIGATOR, University of Virginia

Study Record Dates

2024-12