Effects of Tetrahydrobiopterin (BH4) on Leg Blood Flow and Exercise Capacity in Patients With Peripheral Artery Disease
Status:
Withdrawn
Trial end date:
2020-10-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
University of Nebraska University of Nebraska, Omaha