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Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. Walking exercise is first line therapy to improve walking distance for PAD, but it does not eliminate ischemic leg symptoms in most people with PAD. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. The investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. Participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. As of 2018, only 1.3% of patients with Medicare and symptomatic PAD had enrolled in SET. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. In 2021, the investigators reported that a home-based exercise intervention that incorporated behavioral methods significantly improved six-minute walk in PAD, compared to an attention control group. But no randomized trials have compared SET to a home-based exercise intervention that incorporated behavioral change methods in PAD. However, 45% of people with PAD do not meaningfully respond to exercise interventions, defined as failure to improve six-minute walk by > 20 meters. This phenomenon occurs for both supervised and home-based exercise. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. Therefore, the investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. In this 2 x 2 factorial design, participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Supervised treadmill exercise + nitrate rich beetroot juice | Experimental | This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks. |
|
| Supervised treadmill exercise + placebo | Placebo Comparator | This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks. |
|
| Home-based walking exercise + nitrate rich beetroot juice | Experimental | This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks. |
|
| Home-based walking exercise + placebo | Placebo Comparator | This group will be participating in Home-Based Exercise and drinking placebo beetroot juice with nitrated removed for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Supervised Treadmill Exercise | Behavioral | This is a 12 week intervention where participants will walk for exercise 3 times a week on a treadmill at a center while being supervised by healthcare personnel. |
| Measure | Description | Time Frame |
|---|---|---|
| Six-Minute Walk Distance | Change in six-minute walk distance | Measured at baseline and 12 week follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Walking Impairment Questionnaire (WIQ) Distance Score | WIQ distance score - Range 0-100, 100 is best. | measured at baseline and 12 weeks |
| PROMIS Mobility Questionnaire Score | PROMIS mobility score from administered PROMIS questionnaire. Score range is from zero to infinity and a higher score means a better outcome. |
| Measure | Description | Time Frame |
|---|---|---|
| Physical Activity Step Count | Step count measured over seven days with FITBIT | Measured at baseline and 24 weeks |
| Physical activity distance | Physical activity distance measured over seven days with FITBIT |
Inclusion Criteria:
First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as either:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mary McDermott, MD | Contact | 312-503-6438 | mdm608@northwestern.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University Feinberg School of Medicine | Recruiting | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42035974 | Derived | McDermott MM, Cetlin MD, Domanchuk KJ, Xu S, Whipple MO, Polonsky T, Criqui MH, Guralnik JM, Tian L, Zhao L, Ho KJ, Greenland P, Treat-Jacobson D. Community-based recruitment with ankle brachial index testing to identify peripheral artery disease participants for randomized clinical trials. Am Heart J. 2026 Apr 24;300:107450. doi: 10.1016/j.ahj.2026.107450. Online ahead of print. |
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| ID | Term |
|---|---|
| D058729 | Peripheral Arterial Disease |
| D016491 | Peripheral Vascular Diseases |
| D051346 | Mobility Limitation |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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The investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. In this 2 x 2 factorial design, participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
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For the beetroot juice vs. placebo comparison, this will be a double blinded study where both the participant and the people collecting data will be blinded. For the supervised exercise vs. home-based exercise comparison, the participant and investigator will not be blinded, but the outcomes assessor will be blinded.
| Home-Based Exercise | Behavioral | This is a 12 week intervention where participants will walk at home for exercise with guidance from a study coach. They will have 4 in person visits in the first four weeks and then have weekly phone calls in the last 8 weeks of the intervention with their coach. |
|
| Nitrate-rich beetroot Juice | Dietary Supplement | Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks. |
|
| measured at baseline and 12 weeks |
| 20-meter Improvement in Six-Minute Walk Distance | Meaningful response to exercise interventions | measured at 12 weeks |
| Step Count | Step count measured over seven days with the FITBIT | measured at baseline and 12 weeks |
| Six-Minute Walk Distance | Change in six-minute walk distance | Measured at baseline and 24-week follow up |
| Measured at baseline and 24 weeks. |
| Short physical performance battery (SPPB) | SPPB range, range 0-12, 12-best | measured at baseline and 12 weeks |
| Walking Impairment Questionnaire (WIQ) Stair Climbing Score | WIQ stair climbing score from administered WIQ, range 0-100, 100 is best. | measured at baseline and 12 weeks |
| Walking Impairment Questionnaire (WIQ) Walking Speed Score | WIQ walking speed score from administered WIQ, range 0-100, 100 is best | measured at baseline and 12 weeks |
| Walking Impairment Questionnaire (WIQ) Stair Climbing Score | WIQ stair climbing score from administered WIQ, range 0-100, 100 is best | measured at baseline and 24 weeks |
| Walking Impairment Questionnaire (WIQ) Walking Speed Score | WIQ walking speed score from administered WIQ, range 0-100, 100 is best | measured at baseline and 24 weeks |
| Short physical performance battery (SPPB) | SPPB range, range 0-12, 12-best | measured at baseline and 24 weeks |
| Physical Activity Total Distance | Distance walked over seven days measured with FITBIT | Measured at baseline and 12 weeks |
| University of Chicago | Recruiting | Chicago | Illinois | 60637 | United States |
|
| University of Minnesota | Recruiting | Minneapolis | Minnesota | 55455 | United States |
|
| D002318 |
| Cardiovascular Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |