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

• ClinicalTrials.gov Identifier: NCT02774226
• Recruitment Status: Enrolling by invitation
• First Posted: May 17, 2016
• Last Update Posted: June 20, 2019
• Sponsor: Augusta University
• Information provided by (Responsible Party): Ryan Harris, Augusta University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Tetrahydrobiopterin (BH4); Dietary Supplement: Antioxidant Cocktail	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long Term Nitric Oxide Bioavailability on Vascular Health in Chronic Obstructive Pulmonary Disease
• Study Start Date: September 2015
• Actual Primary Completion Date: January 2019
• Estimated Study Completion Date: January 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tetrahydrobiopterin (BH4); Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline, 4 weeks, 8 weeks, and 12 weeks following, 5mg/kg, 10mg/kg, or 20mg/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); 12 week intervention; Other Name: Kuvan (Sapropterin Dihydrochloride)
Experimental: Antioxidant Cocktail; Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline, 4 weeks, 8 weeks, 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; 12 week intervention; Other Names: Vitamin C; Vitamin E; Alpha Lipoic Acid

Outcome Measures

Primary Outcome Measures :

1. Change in Flow Mediated Dilation [ Time Frame: Change from Baseline, 4 weeks, 8 weeks, and 12 weeks ]

Secondary Outcome Measures :

1. Change in Biomarkers of Oxidative Stress [ Time Frame: Change from Baseline, 4 weeks, 8 weeks, and 12 weeks ]
2. Femoral and Carotid tonometry measurements used to assess Arterial Stiffness [ Time Frame: Change from Baseline, 4 weeks, 8 weeks, and 12 weeks ]
   SphygmoCor Pulse Wave Analysis System (SphygmoCor, PWV Medical, Sydney, Australia), which uses applanation tonometry, will be used for accurate, non-invasive assessment of arterial stiffness. Aortic augmentation index will also be determined and is an index of arterial stiffness.
3. Iontophoresis and Local Heating used to Measure Microvascular Function [ Time Frame: Change from Baseline, 4 weeks, 8 weeks, 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, sodium nitropruside and L-NAME are vasoactive substances that will be used to increase and decrease skin blood flow. The amount of drug delivered is based on the amount of current being delivered. Using this technique with such a low level current, there should be no drug that enters the body.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Georgia Prevention Institute

Augusta, Georgia, United States, 30912

Sponsors and Collaborators

Augusta University

Investigators

• Principal Investigator: Ryan Harris, Ph.D; Augusta University

More Information

• Responsible Party: Ryan Harris, Principal Investigator, Augusta University
• ClinicalTrials.gov Identifier: NCT02774226
• Other Study ID Numbers: COPD-LT
• First Posted: May 17, 2016
• Last Update Posted: June 20, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Ryan Harris, Augusta University:

Flow-Mediated Dilation; Kuvan; Antioxidant; FEV1

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Vitamins; Vitamin E; Thioctic Acid; Antioxidants; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Vitamin B Complex