Peripheral Arterial Disease
Conditions
Keywords
Cardiovascular Diseases, Vascular Diseases, Arterial Occlusive Diseases, Exercise, Functional Capacity
Brief summary
The hypothesis of this proposal is that in subjects with PAD, regular consumption of a high nitrate supplement which raises plasma nitrite, in conjunction with 12 weeks of supervised exercise training at the limb ischemic threshold (SET) will produce a greater clinical benefit (increases in COT and PWT) than placebo plus supervised exercise at the limb ischemic threshold (PET).
Interventions
The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.
The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Peripheral Arterial Disease (ABI of less than 0.9) * Intermittent Claudication for 3 or more months
Exclusion criteria
* Individuals with known alcohol or drug abuse problems * Individuals who have suffered a heart attack or stroke, or have changes on a resting ECG, in the last 3 months * Those classified as American Heart Association Class D * Gangrene, impending limb loss or osteomyelitis * Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months of enrollment * Severe peripheral neuropathy * Any condition other than PAD that limits walking * Chest pain during treadmill exercise which appears before the onset of claudication, or \>3mm ST depression during exercise * Subjects taking nitrates or nitroglycerin products * Must not be taking protein pump inhibitor medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption) | Baseline and 16 Weeks | Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time. |
| Change In Time To Exhaustion | Baseline and 16 weeks | Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Angiogenesis | Baseline and 16 weeks | Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups |
| Change in Functional Ability | Baseline and 16 Weeks | Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test. |
| Change In Claudication Onset Time | Baseline and 16 weeks | Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time. |
| Change In Vascular Function (BAFMD) | Baseline and 16 weeks | Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus . |
Countries
United States
Participant flow
Recruitment details
10,817 patients were screened, 898 potential study candidates were identified, and 32 subjects signed consent and were enrolled from June 2012 through July 2014. Of the 32 subjects who signed consent, 5 subjects were screen failures and 1 withdrew consent. 26 subjects were randomized and 22 subjects completed all study testing.
Participants by arm
| Arm | Count |
|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.
Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training. | 12 |
| BR Juice Placebo and Exercise Training Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.
Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training. | 14 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | BR Juice (Beet-It Stamina Shot) and Exercise Training | BR Juice Placebo and Exercise Training | Total |
|---|---|---|---|
| Age, Continuous | 63.25 years STANDARD_DEVIATION 8.9 | 71.85 years STANDARD_DEVIATION 7.9 | 67.88 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 0 / 14 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 |
Outcome results
Primary
Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption)
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.
Time frame: Baseline and 16 Weeks
Population: All participants who completed study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training | Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption) | 1.48 ml/kg/min | Standard Deviation 2.69 |
| BR Juice Placebo and Exercise Training | Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption) | 0.23 ml/kg/min | Standard Deviation 2.21 |
Primary
Change In Time To Exhaustion
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training | Change In Time To Exhaustion | 289.56 seconds | Standard Deviation 175.44 |
| BR Juice Placebo and Exercise Training | Change In Time To Exhaustion | 254.92 seconds | Standard Deviation 210.48 |
Secondary
Change in Angiogenesis
Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups
Time frame: Baseline and 16 weeks
Population: Participants who had a gastrocnemius muscle biopsy with enough tissue to analyze.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training | Change in Angiogenesis | 0.38 capillaries per fibrer | Standard Deviation 0.54 |
| BR Juice Placebo and Exercise Training | Change in Angiogenesis | 0.26 capillaries per fibrer | Standard Deviation 0.51 |
Secondary
Change In Claudication Onset Time
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training | Change In Claudication Onset Time | 199.22 seconds | Standard Deviation 143.47 |
| BR Juice Placebo and Exercise Training | Change In Claudication Onset Time | 48.58 seconds | Standard Deviation 198.75 |
Secondary
Change in Functional Ability
Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.
Time frame: Baseline and 16 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training | Change in Functional Ability | 172.89 feet | Standard Deviation 166.05 |
| BR Juice Placebo and Exercise Training | Change in Functional Ability | 95 feet | Standard Deviation 173.7 |
Secondary
Change In Vascular Function (BAFMD)
Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .
Time frame: Baseline and 16 weeks
Population: participants with analyzable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) and Exercise Training | Change In Vascular Function (BAFMD) | -1.14 % dilation | Standard Deviation 3.02 |
| BR Juice Placebo and Exercise Training | Change In Vascular Function (BAFMD) | -0.19 % dilation | Standard Deviation 1.8 |