Peripheral Artery Disease
Conditions
Keywords
nitrates, blood flow, vascular function, exercise
Brief summary
The overarching question addressed in the current project is: Does dietary nitrate supplementation (8 weeks) improve physiological function in patients with peripheral arterial disease (PAD)? The investigators will specifically address whether dietary nitrate supplementation enhances blood vessel function, blood pressure regulation, and exercise capacity. The proposed project uses an array of clearly defined measurements which will allow investigators to quantify blood vessel function (vasodilator responsiveness and arterial stiffness), blood pressure (variability and responsiveness to stress), and functional capacity before and after 8 weeks of dietary supplementation.
Interventions
DIETARY_SUPPLEMENTSodium Nitrate
Sodium Nitrate (1g/day) for 8 weeks
OTHERPlacebo
Microcrystalline cellulose (daily) for 8 weeks
Sponsors
American Heart Association
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Documented peripheral artery disease * Ankle-Brachial Index (ABI) \< or = to 0.90
Exclusion criteria
* Non-atherosclerotic vascular disease * Critical limb ischemia * Active ischemic ulceration * Recent (within one year) revascularization * Symptomatic coronary artery disease (angina pectoris) * Heart failure * Resting systolic blood pressure \> 180 mmHg or diastolic pressure \> 100 mmHg * Hypotension (resting systolic BP \< 90 mmHg) * Smoking or history of smoking within past one year * Use of phosphodiesterase V inhibitor drugs * Women with history of hormone replacement therapy within the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vasodilator Capacity | Pre and post 8 weeks of dietary nitrate supplementation | Forearm and calf blood flow will be measured independently by venous occlusion plethysmography using mercury-in-silastic strain gauges. Plethysmographic measurements will be made at rest and following 5 minutes of ischemia (reactive hyperemia) of the distal limb (forearm and calf). Peak blood flow will be determined as the highest flow recorded during the post deflation period. Total blood flow will be measured as the area under the time-curve after resting flow is subtracted. Vascular conductance will be calculated using blood flow/mean arterial pressure (via finger plethysmograph). |
| Change in Arterial Stiffness | Pre and post 8 weeks of dietary nitrate supplementation | ECG gated arterial waveforms will be obtained via applanation tonometry from the carotid and femoral arteries. The pulse wave velocity (PWV; index of arterial stiffness) will be determined between the carotid and femoral measurement sites (cfPWV). The time (t) between the feet of recorded pressure waves will be determined as the mean of 10 consecutive cardiac cycles. PWV is calculated from the distance (D; meters) between measurement points and the measured time delay (t): PWV = D/Δt (m/s). |
| Change in Functional Capacity - Distance Walked in 6 Minutes | Pre and post 8 weeks of dietary nitrate supplementation | 6-minute walk tests will be performed before and after treatment to assess functional capacity. The main comparisons will be changes distance walked in 6 minutes after 8 weeks of dietary nitrate supplementation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Nitrate (NaNO3) Subjects randomized to this group took Sodium Nitrate capsules (1g/day) for 8 weeks | 13 |
| Placebo Subjects randomized to this group took a daily Placebo capsule (Microcrystalline cellulose) for 8 weeks | 8 |
| Total | 21 |
Baseline characteristics
| Characteristic | Sodium Nitrate (NaNO3) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 5 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Continuous | 73 years STANDARD_DEVIATION 9 | 69 years STANDARD_DEVIATION 10 | 72 years STANDARD_DEVIATION 10 |
| Ankle-brachial index (ABI) | 0.76 ratio STANDARD_DEVIATION 0.21 | 0.81 ratio STANDARD_DEVIATION 0.14 | 0.78 ratio STANDARD_DEVIATION 0.18 |
| Body Mass Index | 29.2 kg/m^2 STANDARD_DEVIATION 5.9 | 28.1 kg/m^2 STANDARD_DEVIATION 3.6 | 28.8 kg/m^2 STANDARD_DEVIATION 5.1 |
| Diastolic Blood Pressure | 72 mmHg STANDARD_DEVIATION 9 | 77 mmHg STANDARD_DEVIATION 10 | 74 mmHg STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 13 Participants | 8 Participants | 21 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 9 Participants |
| Systolic Blood Pressure | 136 mmHg STANDARD_DEVIATION 15 | 132 mmHg STANDARD_DEVIATION 13 | 135 mmHg STANDARD_DEVIATION 14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 13 | 0 / 13 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Change in Arterial Stiffness
ECG gated arterial waveforms will be obtained via applanation tonometry from the carotid and femoral arteries. The pulse wave velocity (PWV; index of arterial stiffness) will be determined between the carotid and femoral measurement sites (cfPWV). The time (t) between the feet of recorded pressure waves will be determined as the mean of 10 consecutive cardiac cycles. PWV is calculated from the distance (D; meters) between measurement points and the measured time delay (t): PWV = D/Δt (m/s).
Time frame: Pre and post 8 weeks of dietary nitrate supplementation
Population: We were only able to obtain quality PWV measures in 11 subjects in the sodium nitrate group and 6 in the placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Nitrate (NaNO3) Pre | Change in Arterial Stiffness | 13.8 m/sec | Standard Deviation 3.4 |
| Sodium Nitrate (NaNO3) Post | Change in Arterial Stiffness | 12.8 m/sec | Standard Deviation 2.9 |
| Placebo - Pre | Change in Arterial Stiffness | 10.5 m/sec | Standard Deviation 3.1 |
| Placebo - Post | Change in Arterial Stiffness | 11.0 m/sec | Standard Deviation 3.7 |
Primary
Change in Functional Capacity - Distance Walked in 6 Minutes
6-minute walk tests will be performed before and after treatment to assess functional capacity. The main comparisons will be changes distance walked in 6 minutes after 8 weeks of dietary nitrate supplementation.
Time frame: Pre and post 8 weeks of dietary nitrate supplementation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Nitrate (NaNO3) Pre | Change in Functional Capacity - Distance Walked in 6 Minutes | 387 meters | Standard Deviation 90 |
| Sodium Nitrate (NaNO3) Post | Change in Functional Capacity - Distance Walked in 6 Minutes | 425 meters | Standard Deviation 82 |
| Placebo - Pre | Change in Functional Capacity - Distance Walked in 6 Minutes | 423 meters | Standard Deviation 56 |
| Placebo - Post | Change in Functional Capacity - Distance Walked in 6 Minutes | 427 meters | Standard Deviation 66 |
Primary
Change in Vasodilator Capacity
Forearm and calf blood flow will be measured independently by venous occlusion plethysmography using mercury-in-silastic strain gauges. Plethysmographic measurements will be made at rest and following 5 minutes of ischemia (reactive hyperemia) of the distal limb (forearm and calf). Peak blood flow will be determined as the highest flow recorded during the post deflation period. Total blood flow will be measured as the area under the time-curve after resting flow is subtracted. Vascular conductance will be calculated using blood flow/mean arterial pressure (via finger plethysmograph).
Time frame: Pre and post 8 weeks of dietary nitrate supplementation
Population: Calf blood flow measures were only performed in 11 of the subjects in the NaNO3 group and 7 of the subjects in the Placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Nitrate (NaNO3) Pre | Change in Vasodilator Capacity | Peak forearm Blood Flow | 16.2 ml/100ml tissue/min | Standard Deviation 6.6 |
| Sodium Nitrate (NaNO3) Pre | Change in Vasodilator Capacity | Peak calf Blood Flow | 11.6 ml/100ml tissue/min | Standard Deviation 4.9 |
| Sodium Nitrate (NaNO3) Post | Change in Vasodilator Capacity | Peak calf Blood Flow | 14.1 ml/100ml tissue/min | Standard Deviation 5.1 |
| Sodium Nitrate (NaNO3) Post | Change in Vasodilator Capacity | Peak forearm Blood Flow | 16.4 ml/100ml tissue/min | Standard Deviation 4.2 |
| Placebo - Pre | Change in Vasodilator Capacity | Peak forearm Blood Flow | 16.5 ml/100ml tissue/min | Standard Deviation 5.2 |
| Placebo - Pre | Change in Vasodilator Capacity | Peak calf Blood Flow | 13.1 ml/100ml tissue/min | Standard Deviation 3.5 |
| Placebo - Post | Change in Vasodilator Capacity | Peak forearm Blood Flow | 14.2 ml/100ml tissue/min | Standard Deviation 7.2 |
| Placebo - Post | Change in Vasodilator Capacity | Peak calf Blood Flow | 11.9 ml/100ml tissue/min | Standard Deviation 3.7 |