Long Term Nitric Oxide Bioavailability on Vascular Health in Chronic Obstructive Pulmonary Disease (COPD-LT)

Augusta University

Status and phase: Completed; Phase 2

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Treatments: Drug: Tetrahydrobiopterin (BH4); Dietary Supplement: Antioxidant Cocktail

Study type: Interventional

Funder types: Other

Identifiers

NCT02774226

COPD-LT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

Tetrahydrobiopterin (BH4)

Experimental group

Description:

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.

Treatment:

Drug: Tetrahydrobiopterin (BH4)

Antioxidant Cocktail

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Antioxidant Cocktail