Long Term Nitric Oxide Bioavailability on Vascular Health in Chronic Obstructive Pulmonary Disease

Phase 2

Completed

Interventions: Drug: Tetrahydrobiopterin (BH4)
Dietary Supplement: Antioxidant Cocktail

Brief Summary: Chronic obstructive pulmonary disease (COPD) affects up to 14 million people and is among the top five leading causes of death worldwide. Although COPD is a disease of the lungs, recent evidence indicates that COPD is associated with multiple systemic consequences including vascular endothelial dysfunction. Recently, it has been suggested that more patients with COPD die from cardiovascular disease and coronary heart disease than of direct pulmonary complications. Examination of the mechanisms that contribute to a reduction nitric oxide (NO) bioavailability resulting in vascular endothelial dysfunction in patients with COPD are important as endothelial dysfunction has been indicated to be an independent predictor of future atherosclerotic cardiovascular disease and events.

Detailed Description: Researchers have found a link between chronic obstructive pulmonary disease (COPD) and heart disease; however, a link is all they have found. In a previously funded grant, using a double blind, randomized experimental design, the investigators explored the effect of an acute dose of Kuvan or an antioxidant cocktail (1000mg of vitamin C, 600IU of vitamin E, and 600mg alpha-lipoic acid) on vascular health in patients with COPD. Consequently, the investigators found in separate experiments, that a single dose of both antioxidants and Kuvan transiently improves vascular health in patients with COPD. The current project is an attempt to expand on the investigator's previous findings and explore the effects of sub-chronic use of antioxidants and Kuvan on sustaining the improvements in vascular health in COPD.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Tetrahydrobiopterin (BH4)	Tetrahydrobiopterin (BH4)	Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline and 12 weeks following 5mg/kg of Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4), taken once a day.
Antioxidant Cocktail	Antioxidant Cocktail	Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline and 12 weeks following an anti-oxidant cocktail (vitamin C 1000 mg, vitamin E 400 IU, and alpha lipoic acid 600 mg) taken once a day.

Primary Outcome Measures

Name	Time	Method
Change in Flow Mediated Dilation	Change from Baseline and 12 weeks	Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and 12 weeks after treatment.

Secondary Outcome Measures

Name	Time	Method
FEV1 %Predicted	Change from Baseline and 12 weeks	Forced Expiratory Volume in 1 second. Pulmonary Function Test (PFT).
Percent of ACH to Heat Max	Change from Baseline and 12 weeks	The laser imaging camera is a special camera that shines a low energy laser light on the surface of the skin to measure blood flow. The FLPI makes graphs, photos, and movies of skin blood flow. Acetylcholine is a vasoactive substance that will be used to increase skin blood flow. This variable is the percent of dilation caused by acetylcholine out of the max dilation cause by the warm water bath (44 C).
Change in PWV (Pulse Wave Velocity)	Change from Baseline and 12 weeks	Change in pulse wave velocity (carotid to femoral) as measured using tonometry with the Sphygmocor Xcel system at baseline and after 12 weeks of treatment.