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Effects of Tetrahydrobiopterin (BH4) on Leg Blood Flow and Exercise Capacity in Patients With Peripheral Artery Disease

NCT03493412 · Status: WITHDRAWN · Phase: PHASE4 · Type: INTERVENTIONAL

Last updated 2024-09-03

No results posted yet for this study

Summary

Nitric oxide has been shown to be an important regulator within the cardiovascular system, responsible for regulation of blood flow, blood pressure and vascular growth. Cardiovascular diseases show a reduced ability of the peripheral blood vessels to dilate due to decreased levels of NO with concomitant increased levels of oxidative stress, which is extremely detrimental to patients with PAD, as the limited oxygen delivery to skeletal muscles ultimately results in claudication and reduced physical ability. However, this reduced oxygen delivery and utilization may be able to be improved as previous studies have revealed that tetrahydrobiopterin (BH4), is an important cofactor responsible for NO production. Furthermore, recent studies have shown that endothelial BH4 levels are associated with the vascular pathophysiological response to hypoxia, as it directly mediates endothelial nitric oxide synthase regulation and reduces superoxide production. Additionally, acute administration of BH4 was shown to improve vascular function, specifically, endothelial mediated vasodilatory function, in patients with systemic vascular and coronary disease, as well as six minute walking distances in patients with hypertension. Therefore, the purpose of this proposed study will be to examine the effects of BH4 on vascular function, oxidative stress and leg performance in patients with PAD. This study will examine patients with a classification of stage 1 or stage 2 peripheral artery disease who demonstrate a history of exercise-limiting claudication. Blood vessel oxygen transfer capacity in the leg will be assessed in the femoral and popliteal arteries with ultrasound, and blood vessel dilatory ability will be assessed in the brachial artery with flow-mediated dilation. Skeletal muscle mitochondrial function will be measured with near infrared spectroscopy, and ROS levels will be analyzed through blood samples. Leg function will be measured with an isokinetic dynamometer.

Conditions

Interventions

DRUG

Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)

5 mg/kg will be used as the dose of BH4

DRUG

Placebo

Placebo

Sponsors & Collaborators

  • University of Nebraska

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
CROSSOVER

Eligibility

Min Age
50 Years
Max Age
85 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-07-01
Primary Completion
2019-07-01
Completion
2019-10-01
FDA Drug
Yes

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03493412 on ClinicalTrials.gov