Peripheral Artery DiseasePhase 3IMPACT PADNCT06686121
Improving Mobility After Revascularization in Peripheral Artery Disease
A Phase 3 study testing Home Based Exercise and Nitrate Rich Beetroot Juice in people with Peripheral Artery Disease and Intermittent Claudication, run by Northwestern University at 8 sites in United States.
Trial summary
Lower extremity revascularization combined with supervised exercise significantly improves walking performance compared to revascularization alone in people who have PAD without limb threatening ischemia. However, supervised exercise is inaccessible or burdensome for most PAD patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Artery Disease, Intermittent Claudication, Peripheral Vascular Disease
- What is being tested?
- Home Based Exercise and Nitrate Rich Beetroot Juice
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 386 participants
- Where
- 8 sitesUnited States
- Study dates
- 4 Aug 2025to 1 Aug 2032
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Successful lower extremity revascularization for disabling PAD performed at least 30 days before baseline testing and between 30 and 100 days before randomization.
Who cannot join
- History of leg amputation, not including toe and partial foot amputation
- Active gangrene
- Active limb threatening ischemia
- Already exercising at a level consistent with exercise intervention, using investigator discretion.
- Unstable angina
- Unwilling to drink study beverages
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- Unwilling to adhere to the interventions and complete follow-up testing
- Currently taking sildenafil, tadalafil, or related drugs.
- Unwilling to accept randomization into either group (home-based exercise or attention control)
- Currently consuming beetroot juice, oral nitrate or nitrite, or a beetroot supplement and/or unwilling to avoid beetroot juice during the study. Participants will be asked to discontinue these items for 30 days before baseline testing and throughout the clinical trial. If the potential participant is unwilling to refrain from taking these items, they will not be eligible for the clinical trial.
- History of kidney stones that requires minimized intake of oxalate. Potential participants who need to minimize oxalate intake will be excluded from the trial.
- Baseline blood pressure <100/45.
- Wheelchair confinement or requiring a walker to ambulate
- Walking is limited by a condition other than PAD
- Current foot ulcer
- Planned major surgery, coronary revascularization, or lower extremity revascularization during the next 12 months
- Major medical illness including lung disease requiring oxygen, Parkinson's disease, or a life-threatening illness with life expectancy less than six months.
- Allergy to beetroot juice
- Currently consuming one cup or more of beets daily. Participants will be asked to decrease beet consumption to less than one cup of beets per day for 14 days before baseline testing and throughout the clinical trial. If the potential participant is unwilling to refrain from daily beet consumption of one cup or more for 30 days before the trial and during the trial, they will not be eligible for the clinical trial.
- Participation in or completion of a clinical trial in the previous three months, using investigator discretion for trials that may not impact study participation or outcome measures of the IMPACT PAD Trial.
- Visual impairment that limits walking ability.
- Unable to communicate in English, unless the participant communicates in Spanish and is enrolled at a site that can deliver the intervention in Spanish. All sites with a Spanish speaking coordinator and interventionist will be able to enroll Spanish-speaking participants. While investigators aim to be as inclusive as possible, resources are not available to allow inclusion of people speaking languages that are not Spanish or English.
- Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash determined to be bactericidal and unwilling to discontinue.
- Planning to begin a supervised treadmill exercise program in the next 12 months.
- Heart attack or stroke in previous three months prior to baseline testing.
- An eGFR value <30 or potassium >5.0.
- In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
Emory University School of Medicine
Atlanta, Georgia, 30307
Olamide Alabi, MD
- Recruiting
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Kathryn Domanchuk, BS, 312-503-6438, k-domanchuk@northwestern.edu
Mary M McDermott, MD
- Recruiting
University of Chicago
Chicago, Illinois, 60637
Tamar Polonsky, MD, 773-702-6153
- Recruiting
Henry Ford Health
Detroit, Michigan, 48202
Jonathan Ehrman, PhD
- Recruiting
Rancho Research Institute
Downey, California, 90242
Tze-Woei Tan, MD
- Recruiting
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03766
Philip P Goodney, MD
- Recruiting
University of South Florida
Tampa, Florida, 33606
Ulka Sachdev, MD
- Recruiting
University of Arizona
Tucson, Arizona, 85724
Wei Zhou, MD
About this study
Official title: IMProving Mobility After revasCularizaTion in Peripheral Artery Disease: The IMPACT PAD Trial
Lower extremity revascularization combined with supervised exercise significantly improves walking performance compared to revascularization alone in people who have PAD without limb threatening ischemia. However, supervised exercise is inaccessible or burdensome for most PAD patients. Investigators hypothesize that home-based exercise combined with lower extremity revascularization will significantly improve walking performance compared to revascularization alone in patients with PAD undergoing revascularization for disabling PAD.
Investigators further hypothesize that inorganic nitrate, a major source of nitric oxide (NO) abundant in beetroot juice, will improve walking performance after lower extremity revascularization, compared to placebo. In preclinical models, NO inhibits inflammation, neointimal hyperplasia, thrombosis, and vascular smooth muscle cell migration at sites of revascularization. NO increases angiogenesis and perfusion, repairs skeletal muscle damaged by ischemia, and stimulates mitochondrial activity.
In a randomized clinical trial with a 2 x 2 factorial design, the trial will test the following two primary hypotheses in 386 patients randomized within three months of a successful lower extremity revascularization for disabling PAD: First, that home-based exercise combined with lower extremity revascularization will improve six-minute walk distance more than revascularization alone at 6-month follow-up (Primary Aim #1). Second, that nitrate-rich beetroot juice combined with lower extremity revascularization will improve six-minute walk, compared to placebo combined with revascularization at 6-month follow-up (Primary Aim #2).
Read the detailed description
More than 300,000 surgical or endovascular lower extremity revascularization procedures are performed annually for Medicare beneficiaries who have lower extremity peripheral artery disease (PAD) without limb threatening ischemia, and rates of these procedures are increasing. In these patients, revascularization typically improves, but does not eliminate, PAD related walking impairment. Lower extremity revascularization combined with supervised exercise significantly improves walking performance compared to revascularization alone in people who have PAD without limb threatening ischemia. However, supervised exercise is inaccessible or burdensome for most PAD patients. Investigators hypothesize that home-based exercise combined with lower extremity revascularization will significantly improve walking performance compared to revascularization alone in patients with PAD undergoing revascularization for disabling PAD.
Investigators further hypothesize that inorganic nitrate, a major source of nitric oxide (NO) abundant in beetroot juice, will improve walking performance after lower extremity revascularization, compared to placebo. In preclinical models, NO inhibits inflammation, neointimal hyperplasia, thrombosis, and vascular smooth muscle cell migration at sites of revascularization. NO increases angiogenesis and perfusion, repairs skeletal muscle damaged by ischemia, and stimulates mitochondrial activity. A large body of evidence, assembled over more than 25 years, supports our hypothesis that inorganic nitrate (such as that in nitrate-rich beetroot juice) will improve walking performance and other lower extremity outcomes after lower extremity revascularization.
Effective, accessible, and safe therapies are needed to enhance the benefits and improve durability of lower extremity revascularization. Therefore, in a randomized clinical trial with a 2 x 2 factorial design, the trial will test the following two primary hypotheses in 386 patients randomized within three months of a successful lower extremity revascularization for disabling PAD: First, that home-based exercise combined with lower extremity revascularization will improve six-minute walk distance more than revascularization alone at 6-month follow-up (Primary Aim #1). Second, that nitrate-rich beetroot juice combined with lower extremity revascularization will improve six-minute walk, compared to placebo combined with revascularization at 6-month follow-up (Primary Aim #2). In Secondary Aims, the trial will establish whether home-based exercise, compared to control, and whether nitrate-rich beetroot juice, compared to placebo, improve the Walking Impairment Questionnaire and the PROMIS Mobility Questionnaire and prevent hemodynamic failure of the revascularized vessel. In exploratory aims, the trial will test the effects of the interventions on plasma nitric oxide bioavailability. If our hypotheses are correct, results of this trial will have a major impact on improving mobility in the large and growing number of people undergoing revascularization for disabling PAD.
- Conditions
- Peripheral Artery Disease, Intermittent Claudication, Peripheral Vascular Disease, Mobility Limitation, Revascularization
- Being tested
- Home Based Exercise, Nitrate Rich Beetroot Juice, Attention Control, Placebo Beetroot Juice Without Nitrate
- Keywords
- Behavior Change, Patient Reported Outcome Measures, Mobility, Revascularization, Peripheral artery disease, Intermittent claudication, 6-minute walk, Oxidative stress
- Medical subject headings
- Peripheral Arterial Disease, Intermittent Claudication, Peripheral Vascular Diseases, Mobility Limitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Home Based ExerciseBehavioural
This is a six month intervention where participants will walk at home for exercise with guidance from a study coach. They will attend two to four weekly meetings with the coach at the clinical site in the first 4 weeks following randomization, followed by once weekly telephone coaching calls for the remainder of the six-month intervention
Nitrate Rich Beetroot JuiceDrug
Participants will drink one shot of nitrate rich beet-root juice twice daily for six months.
Attention ControlBehavioural
Participants will be asked to participate in weekly meetings with the coach in the attention control group for weeks 1-26. A staff member will present a topic from the National Institute on Aging "age pages" relevant to health, such as cancer screening or blood pressure treatment. Calls will last approximately 5-15 minutes and will focus on educational topics such as diabetes, healthy eating, and Medicare Part D.
Placebo Beetroot Juice Without NitrateDrug
Participants will drink one shot of placebo beetroot without nitrate juice twice daily for six months.
| Study group | Role | What they receive |
|---|---|---|
| Home based exercise + nitrate rich beetroot juice | Experimental | This group will be participating in home based exercise and drinking nitrate rich beetroot juice for six months. Receives: Behavioral: Home Based Exercise; Drug: Nitrate Rich Beetroot Juice |
| Home-based exercise + placebo | Placebo comparator | This group will be participating in home based exercise and drinking placebo beetroot juice with nitrate removed for six months. Receives: Behavioral: Home Based Exercise; Drug: Placebo Beetroot Juice Without Nitrate |
| Attention control + nitrate-rich beetroot juice | Experimental | This group will be participating in attention control and drinking nitrate rich beetroot juice for six months. Receives: Drug: Nitrate Rich Beetroot Juice; Behavioral: Attention Control |
| Attention control + placebo | Placebo comparator | This group will be participating in attention control and drinking placebo beetroot juice with nitrate removed for six months. Receives: Behavioral: Attention Control; Drug: Placebo Beetroot Juice Without Nitrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-Minute Walk Distance 6-month change
Distance walked in six minutes
Measured: Baseline to 6-month follow-up
Secondary outcomes (6)
Walking Impairment Questionnaire (WIQ) Distance Score 6-month change
Patient reported ability to walk long distances. Score Range 0-100, 100 is best.
Measured: Baseline to 6-month follow-up.
Walking Impairment Questionnaire (WIQ) Distance Score 12-month change
Patient reported ability to walk long distances. Score Range 0-100, 100 is best.
Measured: Baseline to 12-month follow-up
PROMIS Mobility Questionnaire Score 6-month change
Patient report of mobility in daily living. Score range is from zero to infinity and a higher score means a better outcome.
Measured: Baseline to 6-month follow-up
PROMIS Mobility Questionnaire Score 12-month change
Patient report of mobility in daily living. Score range is from zero to infinity and a higher score means a better outcome.
Measured: Baseline to 12-month follow-up.
Prevention of Hemodynamic Failure of The Revascularized Vessel
Hemodynamic failure consists of loss of patency of the revascularized vessel. The outcome will be adjudicated as a categorical outcome. Medical records between randomization and final follow-up will be obtained and reviewed by the IMPACT PAD adjudication committee, consisting of field center investigators and an interventional cardiologist. Participants who meet pre-defined criteria for hemodynamic failure of the revascularized vessel.
Measured: Baseline to 12 month follow-up
Change in 6-minute walk distance
Change in 6-minute walk distance between baseline and 12-month follow-up
Measured: 12 month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2024
- Study start4 Aug 2025
- Primary completion1 Feb 2032 (estimated)
- Study completion1 Aug 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Two x two factorial design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 386 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Rancho Research Institute, Inc., University of Chicago, Wake Forest University, University of Pittsburgh Medical Center, Emory University, University of Arizona, Dartmouth-Hitchcock Medical Center, Henry Ford Health + Michigan State University Health Sciences
- Responsible party
- Principal investigator, Mary McDermott, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06686121
- Sponsor's protocol ID
- STU00222333
- Acronym
- IMPACT PAD
- Status last verified
- Sep 2026
- First submitted
- 8 Nov 2024
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes