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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Tetrahydrobiopterin (BH4)
* Dietary Supplement: Antioxidant Cocktail


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with medically diagnosed COPD apparently healthy controls Exclusion Criteria: FEV1/FVC >0.7 (normal lung function in patients only) Clinical diagnosis of heart disease or diabetes Vasoactive medications (i.e. nitrates, beta-blockers, Viagra etc.) uncontrolled high blood pressure high blood pressure in your lungs thyroid problems Fluid in the lungs Sleep apnea Anemia Raynaud's Phenomenon GI bleeding Gangrene of the digits History of low platelets or coagulopathies Phenylketonuria (PKU) Any allergy to Kuvan

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tetrahydrobiopterin (BH4)<br>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. | Drug: Tetrahydrobiopterin (BH4)<br>* 12 week intervention<br>* Other names: Kuvan (Sapropterin Dihydrochloride);|
| Experimental: Antioxidant Cocktail<br>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. | Dietary Supplement: Antioxidant Cocktail<br>* 12 week intervention<br>* Other names: Alpha Lipoic Acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Flow Mediated Dilation | Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and 12 weeks after treatment. | Change from Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PWV (Pulse Wave Velocity) | 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. | Change from Baseline and 12 weeks | 
| FEV1 %Predicted | Forced Expiratory Volume in 1 second. Pulmonary Function Test (PFT). | Change from Baseline and 12 weeks | 
| Percent of ACH to Heat Max | 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 from Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kuvan, Flow-Mediated Dilation, Antioxidant, FEV1