Peripheral Arterial Disease, Type II Diabetes Mellitus
Conditions
Keywords
Cardiovascular Diseases, Vascular Diseases, Arterial Occlusive Diseases, Diabetes, Exercise, Functional Capacity
Brief summary
The hypothesis of this proposal is that in subjects with Type II diabetes mellitus (T2D) and peripheral arterial disease (PAD) with intermittent claudication (IC), 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 claudication onset time \[COT\] and peak walking time \[PWT\] relative to a group with the same exercise training but supplemented with placebo .This study is essentially exploratory in nature and designed to provide us with information to adequately develop power and execute a larger study. We have previously seen benefits from nitrate supplementation on function in PAD.
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
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Peripheral Arterial Disease (ABI of less than 0.9) * Diagnosed Type II Diabetes * 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 - Maximal Oxygen Capacity (VO2peak) | Baseline & 16 Weeks | Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption |
| Change in Exercise Capacity - Time to Exhaustion (TTE) | Baseline & 16 Weeks | Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Time to Exhaustion (TTE) |
| Change in Exercise Capacity - Claudication Onset Time (COT) | Baseline & 16 Weeks | Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Claudication Onset Time (COT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 Vascular Function | Baseline and 16 weeks | Vascular Function will be measured as the Brachial artery flow-mediated dilation (BAFMD) |
Countries
United States
Participant flow
Recruitment details
6,852 patients in Duke Cardiology and Vascular Surgery Clinics were screened, 392 potential study candidates were identified, and 18 subjects were enrolled from March 2013 through January 2014. Of the 18 subjects, 11 were randomized and 7 completed all study testing.
Participants by arm
| Arm | Count |
|---|---|
| BR Juice (Beet-It Stamina Shot) & Supervised 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) and 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. | 7 |
| 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. | 4 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training | BR Juice Placebo and Exercise Training | Total |
|---|---|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 4.7 | 74.25 years STANDARD_DEVIATION 5.1 | 71.63 years STANDARD_DEVIATION 5.04 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 7 | 0 / 4 |
| serious Total, serious adverse events | 0 / 7 | 0 / 4 |
Outcome results
Primary
Change in Exercise Capacity - Claudication Onset Time (COT)
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Claudication Onset Time (COT)
Time frame: Baseline & 16 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training | Change in Exercise Capacity - Claudication Onset Time (COT) | 189 seconds | Standard Deviation 238.17 |
| BR Juice Placebo and Exercise Training | Change in Exercise Capacity - Claudication Onset Time (COT) | 77.5 seconds | Standard Deviation 36.06 |
Primary
Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak)
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption
Time frame: Baseline & 16 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training | Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak) | 0.85 ml/kg/min | Standard Deviation 0.57 |
| BR Juice Placebo and Exercise Training | Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak) | -0.15 ml/kg/min | Standard Deviation 1.13 |
Primary
Change in Exercise Capacity - Time to Exhaustion (TTE)
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Time to Exhaustion (TTE)
Time frame: Baseline & 16 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training | Change in Exercise Capacity - Time to Exhaustion (TTE) | 196.25 seconds | Standard Deviation 201 |
| BR Juice Placebo and Exercise Training | Change in Exercise Capacity - Time to Exhaustion (TTE) | 247.5 seconds | Standard Deviation 249.61 |
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 underwent the gastrocnemius muscle biopsies
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training | Change in Angiogenesis | 2 ratio of capillaries to muscle fibres | Standard Deviation 0.22 |
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) & Supervised Exercise Training | Change in Functional Ability | 131 feet | Standard Deviation 288.08 |
| BR Juice Placebo and Exercise Training | Change in Functional Ability | 47.5 feet | Standard Deviation 137.89 |
Secondary
Change In Vascular Function
Vascular Function will be measured as the Brachial artery flow-mediated dilation (BAFMD)
Time frame: Baseline and 16 weeks
Population: participants who completed study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training | Change In Vascular Function | 1.83 change % dilation |
| BR Juice Placebo and Exercise Training | Change In Vascular Function | -3.56 change % dilation |