- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01398943
Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)
Regulation of Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease: A Mechanistic Approach
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Georgia
-
Augusta, Georgia, United States, 30912
- Augusta University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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) |
single dose = 5 mg/kg
Other Names:
1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
|
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) |
single dose = 5 mg/kg
Other Names:
1g of vitamin C, 600 IU of vitamin E, and 600 mg of alpha-lipoic acid
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Post FMD was taken approximately 110 min after baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Post PWV was taken approximately 90 min after baseline
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ryan A Harris, PhD, Augusta University
Publications and helpful links
General Publications
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Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AHA00115CS
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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