Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Flow-Mediated Dilation, Kuvan, Antioxidant, FEV1
Brief summary
Chronic obstructive pulmonary disease (COPD) affects up to 14 million people and is among the top five leading causes of death worldwide. Although COPD is a disease of the lungs, recent evidence indicates that COPD is associated with multiple systemic consequences including vascular endothelial dysfunction. Recently, it has been suggested that more patients with COPD die from cardiovascular disease and coronary heart disease than of direct pulmonary complications. Examination of the mechanisms that contribute to a reduction nitric oxide (NO) bioavailability resulting in vascular endothelial dysfunction in patients with COPD are important as endothelial dysfunction has been indicated to be an independent predictor of future atherosclerotic cardiovascular disease and events.
Detailed description
Researchers have found a link between chronic obstructive pulmonary disease (COPD) and heart disease; however, a link is all they have found. In a previously funded grant, using a double blind, randomized experimental design, the investigators explored the effect of an acute dose of Kuvan or an antioxidant cocktail (1000mg of vitamin C, 600IU of vitamin E, and 600mg alpha-lipoic acid) on vascular health in patients with COPD. Consequently, the investigators found in separate experiments, that a single dose of both antioxidants and Kuvan transiently improves vascular health in patients with COPD. The current project is an attempt to expand on the investigator's previous findings and explore the effects of sub-chronic use of antioxidants and Kuvan on sustaining the improvements in vascular health in COPD.
Interventions
12 week intervention
DIETARY_SUPPLEMENTAntioxidant Cocktail
12 week intervention
Sponsors
Augusta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* patients with medically diagnosed COPD * apparently healthy controls
Exclusion criteria
* FEV1/FVC \>0.7 (normal lung function in patients only) * Clinical diagnosis of heart disease or diabetes * Vasoactive medications (i.e. nitrates, beta-blockers, Viagra etc.) * uncontrolled high blood pressure * high blood pressure in your lungs * thyroid problems * Fluid in the lungs * Sleep apnea * Anemia * Raynaud's Phenomenon * GI bleeding * Gangrene of the digits * History of low platelets or coagulopathies * Phenylketonuria (PKU) * Any allergy to Kuvan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Flow Mediated Dilation | Change from Baseline and 12 weeks | Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and 12 weeks after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PWV (Pulse Wave Velocity) | Change from Baseline and 12 weeks | Change in pulse wave velocity (carotid to femoral) as measured using tonometry with the Sphygmocor Xcel system at baseline and after 12 weeks of treatment. |
| FEV1 %Predicted | Change from Baseline and 12 weeks | Forced Expiratory Volume in 1 second. Pulmonary Function Test (PFT). |
| Percent of ACH to Heat Max | Change from Baseline and 12 weeks | The laser imaging camera is a special camera that shines a low energy laser light on the surface of the skin to measure blood flow. The FLPI makes graphs, photos, and movies of skin blood flow. Acetylcholine is a vasoactive substance that will be used to increase skin blood flow. This variable is the percent of dilation caused by acetylcholine out of the max dilation cause by the warm water bath (44 C). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tetrahydrobiopterin (BH4) Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline, 4 weeks, 8 weeks, and 12 weeks following, 5mg/kg, 10mg/kg, or 20mg/kg of Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4), taken once a day.
Tetrahydrobiopterin (BH4): 12 week intervention | 8 |
| Antioxidant Cocktail Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline, 4 weeks, 8 weeks, and 12 weeks following an anti-oxidant cocktail (vitamin C 1000 mg, vitamin E 400 IU, and alpha lipoic acid 600 mg) taken once a day.
Antioxidant Cocktail: 12 week intervention | 7 |
| Total | 15 |
Baseline characteristics
| Characteristic | Antioxidant Cocktail | Total | Tetrahydrobiopterin (BH4) |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 6 | 59 years STANDARD_DEVIATION 5 | 61 years STANDARD_DEVIATION 5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 0 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Change in Flow Mediated Dilation
Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and 12 weeks after treatment.
Time frame: Change from Baseline and 12 weeks
Population: Data was not usable on one participant in the antioxidant group. Too much artifact.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetrahydrobiopterin (BH4) | Change in Flow Mediated Dilation | 0.26 percentage of flow mediated dilation | Standard Deviation 2.57 |
| Antioxidant Cocktail | Change in Flow Mediated Dilation | -1.5 percentage of flow mediated dilation | Standard Deviation 3.86 |
Secondary
Change in PWV (Pulse Wave Velocity)
Change in pulse wave velocity (carotid to femoral) as measured using tonometry with the Sphygmocor Xcel system at baseline and after 12 weeks of treatment.
Time frame: Change from Baseline and 12 weeks
Population: Unable to obtain pulse wave on 2 participants in the AOX group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetrahydrobiopterin (BH4) | Change in PWV (Pulse Wave Velocity) | -0.36 m/s | Standard Deviation 0.66 |
| Antioxidant Cocktail | Change in PWV (Pulse Wave Velocity) | 0.34 m/s | Standard Deviation 0.86 |
Secondary
FEV1 %Predicted
Forced Expiratory Volume in 1 second. Pulmonary Function Test (PFT).
Time frame: Change from Baseline and 12 weeks
Population: Unable to obtain valid lung function on one participant in the BH4 group as well as one participant in the AOX group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetrahydrobiopterin (BH4) | FEV1 %Predicted | -3.6 percentage of predicted | Standard Deviation 6.3 |
| Antioxidant Cocktail | FEV1 %Predicted | -4.2 percentage of predicted | Standard Deviation 10.9 |
Secondary
Percent of ACH to Heat Max
The laser imaging camera is a special camera that shines a low energy laser light on the surface of the skin to measure blood flow. The FLPI makes graphs, photos, and movies of skin blood flow. Acetylcholine is a vasoactive substance that will be used to increase skin blood flow. This variable is the percent of dilation caused by acetylcholine out of the max dilation cause by the warm water bath (44 C).
Time frame: Change from Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetrahydrobiopterin (BH4) | Percent of ACH to Heat Max | 4.2 percent | Standard Deviation 15 |
| Antioxidant Cocktail | Percent of ACH to Heat Max | -0.8 percent | Standard Deviation 41.6 |