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Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01398943
First Posted: July 21, 2011
Last Update Posted: September 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Ryan Harris, Augusta University
July 19, 2011
July 21, 2011
November 17, 2016
July 25, 2017
September 13, 2017
September 2010
June 2015   (Final data collection date for primary outcome measure)
Flow-Mediated Dilation (FMD) [ Time Frame: Post FMD was taken approximately 110 min after baseline ]
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function at baseline and several hours after each experimental intervention.
Flow-Mediated Dilation (FMD) [ Time Frame: 1-4 days ]
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function at baseline and several hours after each experimental intervention.
Complete list of historical versions of study NCT01398943 on ClinicalTrials.gov Archive Site
Pulse Wave Velocity [ Time Frame: Post PWV was taken approximately 90 min after baseline ]
A measure of vascular stiffness at baseline and several hours after each experimental intervention.
Active Hyperemia Induced Flow-Mediated Dilation [ Time Frame: 1-4 days ]
Active hyperemia induced via localized exercise eliminates the systemic pulmonary limintation and allows for the assessment of skeletal muscle function.
Not Provided
Not Provided
 
Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)
Regulation of Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease: A Mechanistic Approach
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.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Pulmonary Disease, Chronic Obstructive
  • Drug: Tetrahydrobiopterin (BH4)
    single dose = 5 mg/kg
    Other Name: Kuvan (Sapropterin Dihydrochloride)
  • Dietary Supplement: Antioxidant Cocktail
    1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
  • Experimental: 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)

    Interventions:
    • Drug: Tetrahydrobiopterin (BH4)
    • Dietary Supplement: Antioxidant Cocktail
  • Experimental: 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)

    Interventions:
    • Drug: Tetrahydrobiopterin (BH4)
    • Dietary Supplement: Antioxidant Cocktail

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
June 2015
June 2015   (Final data collection date for primary outcome measure)

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

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01398943
AHA00115CS
Yes
Not Provided
Plan to Share IPD: Yes
Ryan Harris, Augusta University
Augusta University
American Heart Association
Principal Investigator: Ryan A Harris, PhD Augusta University
Augusta University
August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP