A Phase 3 interventional study of Home Based Exercise and Nitrate Rich Beetroot Juice in Peripheral Artery Disease, Intermittent Claudication and Peripheral Vascular Disease, sponsored by Northwestern University. Recruiting at 8 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-05.
Sponsored by Northwestern University · Phase 3, Interventional, and Treatment
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).
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.
309 studies on the registry are indexed under Intermittent Claudication; 46 are open to participants now.
This study's planned enrollment of 386 is above the median of 74 across 242 interventional studies indexed under Intermittent Claudication.
Browse Intermittent Claudication studies →Northwestern University is the lead sponsor of 1,423 studies on the registry; 198 are open to participants now.
Of its 105 completed or terminated interventional studies of FDA-regulated products, 78 (74%) have results posted.
Compared within Intermittent Claudication, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Peripheral Arterial Disease. The counts are of registry records indexed under each term, refreshed daily. How we classify →
The criteria were revised on the registry on Oct 5, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Successful lower extremity revascularization for disabling PAD performed at least 30 days before baseline testing and between 30 and 100 days before randomization.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This group will be participating in home based exercise and drinking nitrate rich beetroot juice for six months.
Behavioral: Home Based Exercise · Drug: Nitrate Rich Beetroot Juice
This group will be participating in home based exercise and drinking placebo beetroot juice with nitrate removed for six months.
Behavioral: Home Based Exercise · Drug: Placebo Beetroot Juice Without Nitrate
This group will be participating in attention control and drinking nitrate rich beetroot juice for six months.
Drug: Nitrate Rich Beetroot Juice · Behavioral: Attention Control
This group will be participating in attention control and drinking placebo beetroot juice with nitrate removed for six months.
Behavioral: Attention Control · Drug: Placebo Beetroot Juice Without Nitrate
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
Participants will drink one shot of nitrate rich beet-root juice twice daily for six months.
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.
Participants will drink one shot of placebo beetroot without nitrate juice twice daily for six months.
Six-Minute Walk Distance 6-month change
Distance walked in six minutes
Time frame: Baseline to 6-month follow-up
Walking Impairment Questionnaire (WIQ) Distance Score 6-month change
Patient reported ability to walk long distances. Score Range 0-100, 100 is best.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 12 month follow-up
Six-Minute Walk Distance
Change in six-minute walk distance 24 hours after the final study beverage
Time frame: Baseline to six-month follow-up at the time point that is twenty-four hours after the final study drink
Plasma Nitrite Levels
Change in plasma nitrite levels in the blood at 6-month follow-up
Time frame: Baseline to 6-month follow-up
BH4/BH2 6-month change
Change in BH4/BH2 ratio
Time frame: Baseline to 6-month follow-up
Progression of PAD
Determine whether home-based walking exercise, compared to attention control prevents progression of PAD, defined by any new lower extremity revascularization, acute limb ischemia, or amputation of either lower extremity between baseline and 12-month follow-up.
Time frame: Baseline to 12-month follow-up
Plan to share: Yes
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data will be available at the time the primary outcome manuscript is submitted for publication and will be available for up to 10 years.
Access criteria: Per BioLINCC
No publications or documents are linked to this record.
Started Aug 2025 (actual). Primary completion is estimated for Feb 2032, 77 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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