Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Georgia Regents University
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Ryan Harris, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01398943
First received: July 19, 2011
Last updated: March 27, 2014
Last verified: March 2014

July 19, 2011
March 27, 2014
September 2010
June 2014   (final data collection date for primary outcome measure)
Flow-Mediated Dilation (FMD) [ Time Frame: 1-4 days ] [ Designated as safety issue: No ]
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function at baseline and several hours after each experimental intervention.
Same as current
Complete list of historical versions of study NCT01398943 on ClinicalTrials.gov Archive Site
Active Hyperemia Induced Flow-Mediated Dilation [ Time Frame: 1-4 days ] [ Designated as safety issue: No ]
Active hyperemia induced via localized exercise eliminates the systemic pulmonary limintation and allows for the assessment of skeletal muscle function.
Same as current
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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Pulmonary Disease, Chronic Obstructive
  • Drug: Tetrahydrobiopterin (BH4)
    single dose = 5 mg/kg
    Other Name: Kuvan (Sapropterin Dihydrochloride)
  • Drug: non-acetylated salicylate
    3,000 mg per day for 4 days
    Other Name: Salsalate
  • Dietary Supplement: High Fat Meal
    The high-fat meal ([900 calories], 50 g of fat, 14 g of saturated fat, 225 mg of cholesterol) will consist of an Egg McMuffin®, Sausage McMuffin®, and two hash brown patties (McDonald's Corporation®). Additional water will be allowed ad libidum. The P.I. along with others have used this meal to attenuate FMD in healthy adults with the mechanism suggested to be through an increase in lipemia induced oxidative stress.
  • Drug: L-NMMA
    dosage range = 4 mg/kg/min
  • Dietary Supplement: Antioxidant Cocktail
    1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
  • Experimental: Increase in NO Bioavailability
    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 (BH4).
    Intervention: Drug: Tetrahydrobiopterin (BH4)
  • Experimental: Decrease in NO Bioavailability
    Brachial artery flow-mediated dilation (FMD), markers of inflammation, and markers of oxidative stress will be assessed at baseline and following a decrease in nitric oxide bioavailability (high fat meal).
    Intervention: Dietary Supplement: High Fat Meal
  • Experimental: Inhibition of NO
    Brachial artery flow-mediated dilation (FMD), markers of inflammation, and markers of oxidative stress will be assessed at baseline and following competitive inhibition of nitric oxide production (L-NMMA).
    Intervention: Drug: L-NMMA
  • Experimental: Inhibition of Inflammation
    Brachial artery flow-mediated dilation and biomarkers of inflammation (IL-6, IL-1β, TNF-α, NF-kβ) will be assessed at baseline and following 4 days of therapeutic doses (3,000 mg per day) of Salsalate (non-acetylated salicylate) treatment or placebo. This treatment dose is the standard therapy prescribed for patients with inflammatory arthritis.
    Intervention: Drug: non-acetylated salicylate
  • Experimental: Inhibition of Oxidative Stress
    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.)
    Intervention: Dietary Supplement: Antioxidant Cocktail

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
240
Not Provided
June 2014   (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
Both
18 Years and older
Yes
Contact: Ryan A Harris, PhD 706-721-5998 ryharris@gru.edu
Contact: Nichole Siegler, BS 706-721-5998 masiegler@gru.edu
United States
 
NCT01398943
AHA00115CS
Yes
Ryan Harris, Georgia Regents University
Georgia Regents University
American Heart Association
Principal Investigator: Ryan A Harris, PhD Georgia Regents University
Georgia Regents University
March 2014

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