Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD)
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| ClinicalTrials.gov Identifier: NCT01398943 |
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Recruitment Status :
Completed
First Posted : July 21, 2011
Results First Posted : July 25, 2017
Last Update Posted : December 11, 2017
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pulmonary Disease, Chronic Obstructive | Drug: Tetrahydrobiopterin (BH4) Dietary Supplement: Antioxidant Cocktail | Not Applicable |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | Regulation of Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease: A Mechanistic Approach |
| Study Start Date : | September 2010 |
| Actual Primary Completion Date : | June 2015 |
| Actual Study Completion Date : | June 2015 |
| Arm | Intervention/treatment |
|---|---|
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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) |
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 |
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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) |
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 |
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01398943
| United States, Georgia | |
| Augusta University | |
| Augusta, Georgia, United States, 30912 | |
| Principal Investigator: | Ryan A Harris, PhD | Augusta University |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Ryan Harris, Assistant Professor, Director Laboratory of Integrative Vascular and Exercise Physiology, Augusta University |
| ClinicalTrials.gov Identifier: | NCT01398943 |
| Other Study ID Numbers: |
AHA00115CS |
| First Posted: | July 21, 2011 Key Record Dates |
| Results First Posted: | July 25, 2017 |
| Last Update Posted: | December 11, 2017 |
| Last Verified: | November 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
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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 |
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Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases |
Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs |