Clinical trial NCT01398943: Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)
Official title: Regulation of Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease: A Mechanistic Approach
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2011-07-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Flow-Mediated Dilation (FMD)
timeFrame: Post FMD was taken approximately 110 min after baseline
Secondary outcomes:
measure: Pulse Wave Velocity
timeFrame: Post PWV was taken approximately 90 min after baseline
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Augusta University
state: Georgia
Study officials:
affiliation: Augusta University
name: Ryan A Harris, PhD
role: PRINCIPAL_INVESTIGATOR
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