BEETroot Juice to Reverse Functional Impairment in PAD

NCT05624125 | Recruiting DMC

• 2 other identifiers: STU00217101R01AG073257
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 4

Brief Summary

The BEET PAD Trial is a multi-centered double-blind randomized clinical trial designed to determine whether beetroot juice, compared to placebo, improves six-minute walk distance at four month follow-up in people with lower extremity peripheral artery disease (PAD). Investigators hypothesize that by simultaneously increasing lower extremity perfusion, gastrocnemius muscle mitochondrial activity, and myofiber health and regeneration, beetroot juice will significantly improve walking performance in people with PAD. The primary aim is to determine whether beetroot juice significantly improves six-minute walk distance at 4-month follow-up in people with PAD, compared to placebo. Preliminary evidence suggests that beetroot juice has both acute and chronic effects on walking performance in PAD. The primary outcome will measure the combined acute and chronic effect of beetroot juice (i.e. the maximal effect) on change in 6-minute walk at 4-month follow-up. In secondary aims, investigators will distinguish between acute and chronic effects of beetroot juice on six-minute walk and delineate biologic pathways by which beetroot juice improves walking performance in PAD, by measuring change in gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health. The trial will assess the durability of beetroot juice effects on six-minute walk. Nitrate in beetroot juice is metabolized to nitrite and subsequently to NO, attaining peak nitrite levels 2.5 hours after ingestion. The trial will determine whether a higher peak or a greater increase in plasma nitrite at 2.5 hours after beetroot juice consumption at baseline has a greater effect on six-minute walk at 4-month follow-up, compared to a lower peak or a smaller increase, respectively.

Conditions

Peripheral Artery Disease

Keywords

beetroot juice, mobility, intermittent claudication, peripheral artery disease

Outcome Measures

Primary Outcomes (1)

• Four-month change in six-minute walk distance

  Change in six-minute walk distance at four-month follow-up will be compared between those randomized to beetroot juice vs. those randomized to placebo

  Baseline to four-month follow-up

Secondary Outcomes (5)

• 2.5 hour change in six-minute walk distance (acute effect)

  Baseline 2.5 hour follow-up

• Four-month + 24 hour change in six-minute walk distance (chronic effect)

  Baseline to four-month + 24 hour follow-up

• Four-month change in calf muscle perfusion

  Baseline to four-month follow-up

• Four-month change in Walking Impairment Questionnaire (WIQ) distance score

  Baseline to four-month follow-up

• Four-month change in six-minute walk distance among participants randomized to beetroot juice

  2.5 hour to four-month follow-up

Other Outcomes (6)

• Durability of effect on six-minute walk distance

  14 days after the end of the assigned study drink (intervention or placebo)

• Four-month change in Walking Impairment Questionnaire (WIQ) speed and stair climbing scores

  Baseline to four-month follow-up

• Four-month change in Short-Form 36 Physical Function questionnaire score

  Baseline to four-month follow-up

Study Arms (2)

Beetroot juice

ACTIVE COMPARATOR

The beetroot juice intervention comes in a single 70 ml drink and is manufactured by James White Drinks. Each drink contains beetroot juice and 2% lemon juice, made from concentrates. Each serving of 70 mL of beetroot juice contains 400 mgs (6.45 millimoles) of nitrate and will be taken twice daily for a total daily dose of 800 mgs (12.90 millimoles) of nitrate.

Other: Beetroot juice

Placebo

PLACEBO COMPARATOR

The placebo comes in a single 70 ml drink and is manufactured by James White Drinks. The placebo contains beetroot juice and 2% lemon juice, made from concentrates, and is filtered to remove nitrate.

Other: Placebo

Interventions

Beetroot juice OTHER

Two 70 ml beetroot juice drinks daily for 4 months.

Beetroot juice

Placebo OTHER

Two 70 ml placebo drinks daily for 4 months.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50 and older
• Presence of peripheral artery disease, defined as:
• An ankle brachial index (ABI) \<= 0.90 at baseline
• Vascular lab evidence of PAD (such as a toe brachial pressure \<= 0.70 or an ankle brachial index \<=0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities.
• An ABI of \>0.90 and \<=1.00 who experience a 20% or greater drop in ABI in either leg after the heel-rise test.

You may not qualify if:

• Above- or below-knee amputation
• Critical limb ischemia defined as an ABI \<0.40 with symptoms of rest pain
• Wheelchair confinement or requiring a walker to ambulate
• Walking is limited by a symptom other than PAD
• Current foot ulcer on bottom of foot
• Failure to successfully complete the study run-in
• Planned major surgery, coronary or leg revascularization during the next five months
• Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
• Major medical illness including lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
• Mini-Mental Status Examination (MMSE) score \< 23
• Allergy to beetroot juice
• 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.
• Currently consuming one cup or more of beets daily. Participants will be asked to discontinue beet ingestion of one cup or more of beets for 30 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.
• Non-English speaking
• Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]

Sponsors & Collaborators

• Northwestern University: lead
• University of Virginia: collaborator
• University of Chicago: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (4)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Mary McDermott, MD

CONTACT

312-503-6419; mdm608@northwestern.edu

Kathryn Domanchuk, BS

CONTACT

312-503-6438; k-domanchuk@northwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jeremiah Stamler Professor of Medicine

Study Record Dates

• First Submitted: November 13, 2022
• First Posted: November 21, 2022
• Study Start: January 25, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)