Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)

NCT01398943 | Completed Results DMC

• 1 other identifier: AHA00115CS
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

More patients with chronic obstructive pulmonary disease (COPD) die from cardiovascular disease than direct pulmonary complications. Inflammation and oxidative stress, characteristic in COPD, are likely contributors to the reduction in nitric oxide (NO) bioavailability and vascular endothelial dysfunction in COPD patients; however, this has yet to be determined. Thus, the overall objective of this proposal is to identify the role of NO bioavailability in contributing to vascular endothelial dysfunction in patients with COPD and to provide insight into the molecular mechanisms involved. Our central hypothesis is that inflammation and oxidative stress, both independently, contribute to the reduction in NO bioavailability and vascular endothelial dysfunction in patients with COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

flow-mediated dilation; arterial stiffness; intima-media thickness; pulse wave velocity; dual energy x-ray absorptiometry; inflammatory markers; blood lipids; tetrahydrobiopterin; body mass index; hemoglobin A1c; complete blood count; oxidative stress biomarkers; pulmonary function test; lung; COPD

Outcome Measures

Primary Outcomes (1)

• Flow-Mediated Dilation (FMD)

  Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function at baseline and several hours after each experimental intervention.

  Post FMD was taken approximately 110 min after baseline

Secondary Outcomes (1)

• Pulse Wave Velocity

  Post PWV was taken approximately 90 min after baseline

Study Arms (2)

COPD Patients

EXPERIMENTAL

Patients with COPD AOC protocol: Brachial artery flow-mediated dilation, direct assessment of oxidative stress via EPR spectroscopy (O2-) and biomarkers of oxidative stress (8-isoprostane, LH, SOD) will be assessed at baseline and 2 hours following ingestion of a single oral antioxidant cocktail (1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid.) Antioxidant Cocktail: 1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid BH4 protocol: Brachial artery flow-mediated dilation (FMD), markers of inflammation, and markers of oxidative stress will be assessed at baseline and following an increase in nitric oxide bioavailability after administering a single dose = 5 mg/kg of Tetrahydrobiopterin (BH4)

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

Controls

EXPERIMENTAL

Healthy age- and sex- matched controls AOC protocol: Brachial artery flow-mediated dilation, direct assessment of oxidative stress via EPR spectroscopy (O2-) and biomarkers of oxidative stress (8-isoprostane, LH, SOD) will be assessed at baseline and 2 hours following ingestion of a single oral antioxidant cocktail (1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid.) Antioxidant Cocktail: 1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid BH4 protocol: Brachial artery flow-mediated dilation (FMD), markers of inflammation, and markers of oxidative stress will be assessed at baseline and following an increase in nitric oxide bioavailability after administering a single dose = 5 mg/kg of Tetrahydrobiopterin (BH4)

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

Interventions

Tetrahydrobiopterin (BH4) DRUG

single dose = 5 mg/kg

Also known as: Kuvan (Sapropterin Dihydrochloride)

COPD Patients; Controls

Antioxidant Cocktail DIETARY_SUPPLEMENT

1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid

COPD Patients; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with COPD (GOLD stages II-IV) and matched healthy controls
• Caucasian or African American
• Both men and women
• Current and former smokers

You may not qualify if:

• GOLD Stage I
• Clinical diagnosis of heart disease, hypertension, or metabolic disease
• Vasoactive medications (i.e. nitrates, beta-blockers, ACE inhibitors, Viagra, etc.)
• Pulmonary hypertension
• Hypothyroidism
• Hyper-homocysteinemia
• Interstitial lung disease
• Phenylketonuria
• Pregnancy
• Sleep apnea
• Anemia
• Raynod's phenomenon
• Gangrene of the digits
• History of low platelets or coagulopathies
• Aspirin sensitivity or allergy

Sponsors & Collaborators

• Augusta University: lead
• American Heart Association: collaborator

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

Location

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  PMID: 29705218 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Ryan Harris, Ph.D.
• Organization: Augusta University

ryharris@augusta.edu

706-721-5998

Study Officials

• Ryan A Harris, PhD

  Augusta University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Director Laboratory of Integrative Vascular and Exercise Physiology

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: July 21, 2011
• Study Start: September 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: December 11, 2017
• Results First Posted: July 25, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)