Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)
NCT ID: NCT01398943
Last Updated: 2017-12-11
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
NA
Total Enrollment
60 participants
Study Classification
INTERVENTIONAL
Study Start Date
2010-09-30
Study Completion Date
2015-06-30
Brief Summary
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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.
Detailed Description
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Flow-Mediated Dilation (FMD) - Subjects will lie in the supine position for 20 minutes to obtain hemodynamic steady state. A blood pressure cuff (Hokanson) will be placed around the forearm (distal to the Doppler transducer) and rapidly inflated to 250 mmHg for 5 minutes (circulatory arrest). Simultaneous ultrasound images of the vessel (B-mode) and Doppler waveforms will be collected 10 seconds prior to and for 2 minutes following deflation of the cuff. All B-mode images will be analyzed using automated edge detection software (Medical Imaging Applications), while intensity weighted velocity spectra segments will be saved to the GE Logiq 7 hard drive for off-line blood velocity waveform analysis. P.I. has utilized the traditional method of brachial artery flow-mediated dilation (FMD) induced by reactive hyperemia to assess vascular endothelial function in populations ranging from young healthy adults to older adults with pathological conditions.
Spygmocor - Pulse Wave Velocity (PWV) - A Spygmocor® device will be used at baseline and following each protocol to assess PWV. PWV analysis provides a non-invasive assessment of arterial stiffness. Increased arterial stiffness is known to be associated with cardiovascular disease. The participant is required to lie in a resting position for approximately 30-45 minutes. The research assistant will place ECG electrode sensors at the carotid, femoral, radial and distal artery locations. A highly sensitive pen-like device, called a tonometer, is then gently applied to record the velocity of the blood flow between each of the points.
Spygmocor - Pulse Wave Velocity (PWV) - A Spygmocor® device will be used at baseline and following each protocol to assess PWV. PWV analysis provides a non-invasive assessment of arterial stiffness. Increased arterial stiffness is known to be associated with cardiovascular disease. The participant is required to lie in a resting position for approximately 30-45 minutes. The research assistant will place ECG electrode sensors at the carotid, femoral, radial and distal artery locations. A highly sensitive pen-like device, called a tonometer, is then gently applied to record the velocity of the blood flow between each of the points.
Conditions
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Pulmonary Disease, Chronic Obstructive
Keywords
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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
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
CROSSOVER
Primary Study Purpose
PREVENTION
Blinding Strategy
DOUBLE
Participants
Investigators
Study Groups
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COPD Patients
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)
Group Type
EXPERIMENTAL
Tetrahydrobiopterin (BH4)
Intervention Type
DRUG
single dose = 5 mg/kg
Antioxidant Cocktail
Intervention Type
DIETARY_SUPPLEMENT
1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
Controls
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)
Group Type
EXPERIMENTAL
Tetrahydrobiopterin (BH4)
Intervention Type
DRUG
single dose = 5 mg/kg
Antioxidant Cocktail
Intervention Type
DIETARY_SUPPLEMENT
1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
Interventions
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Tetrahydrobiopterin (BH4)
single dose = 5 mg/kg
Intervention Type
DRUG
Antioxidant Cocktail
1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
Intervention Type
DIETARY_SUPPLEMENT
Other Intervention Names
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Kuvan (Sapropterin Dihydrochloride)
Eligibility Criteria
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Inclusion Criteria
* Patients with COPD (GOLD stages II-IV) and matched healthy controls
* Caucasian or African American
* Both men and women
* Current and former smokers
* Caucasian or African American
* Both men and women
* Current and former smokers
Exclusion Criteria
* 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
* 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
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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American Heart Association
OTHER
Sponsor Role
collaborator
Augusta University
OTHER
Sponsor Role
lead
Responsible Party
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Ryan Harris
Assistant Professor, Director Laboratory of Integrative Vascular and Exercise Physiology
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Ryan A Harris, PhD
Role: PRINCIPAL_INVESTIGATOR
Augusta University
Locations
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Augusta University
Augusta, Georgia, United States
Site Status
Countries
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United States
References
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Rodriguez-Miguelez P, Gregg J, Seigler N, Bass L, Thomas J, Pollock JS, Sullivan JC, Dillard TA, Harris RA. Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD. Chest. 2018 Sep;154(3):597-606. doi: 10.1016/j.chest.2018.04.028. Epub 2018 Apr 26.
Reference Type
DERIVED
Other Identifiers
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AHA00115CS
Identifier Type: -
Identifier Source: org_study_id