Clinical trial NCT05624125: BEETroot Juice to Reverse Functional Impairment in PAD
Official title: BEETroot Juice to Reverse Functional Impairment in PAD: The BEET PAD Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Artery Disease
Keywords: beetroot juice, mobility, intermittent claudication, peripheral artery disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: University of Virginia
name: University of Chicago
name: National Institute on Aging (NIA)
First posted: 2022-11-21
Enrollment: 210
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age 50 and older
2. Presence of peripheral artery disease, defined as:

   1. An ankle brachial index (ABI) \<= 0.90 at baseline
   2. 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.
   3. 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.

Exclusion Criteria:

1. Above- or below-knee amputation
2. Critical limb ischemia defined as an ABI \<0.40 with symptoms of rest pain
3. Wheelchair confinement or requiring a walker to ambulate
4. Walking is limited by a symptom other than PAD
5. Current foot ulcer on bottom of foot
6. Failure to successfully complete the study run-in
7. Planned major surgery, coronary or leg revascularization during the next five months
8. Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
9. 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
10. Mini-Mental Status Examination (MMSE) score \< 23
11. Allergy to beetroot juice
12. 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.
13. 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.
14. Non-English speaking
15. Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]
16. Visual impairment that limits walking ability.
17. Six-minute walk distance of \<500 feet or \>1600 feet. Investigator discretion will be used to decide whether participants who walk greater than 1600 feet are eligible.
18. Baseline blood pressure \<100/45.
19. Participation in a supervised treadmill exercise program in previous three months.
20. Using an antibacterial mouthwash (such as Cepacol) or a mouthwash containing chlorhexidine and unwilling to discontinue.
21. 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.

Primary outcomes:
measure: Four-month change in six-minute walk distance
timeFrame: Baseline to four-month follow-up
Secondary outcomes:
measure: 2.5 hour change in six-minute walk distance (acute effect)
timeFrame: Baseline 2.5 hour follow-up
measure: Four-month + 24 hour change in six-minute walk distance (chronic effect)
timeFrame: Baseline to four-month + 24 hour follow-up
measure: Four-month change in calf muscle perfusion
timeFrame: Baseline to four-month follow-up
measure: Four-month change in Walking Impairment Questionnaire (WIQ) distance score
timeFrame: Baseline to four-month follow-up
measure: Four-month change in six-minute walk distance among participants randomized to beetroot juice
timeFrame: 2.5 hour to four-month follow-up
Other outcomes:
measure: Durability of effect on six-minute walk distance
timeFrame: 14 days after the end of the assigned study drink (intervention or placebo)
measure: Four-month change in Walking Impairment Questionnaire (WIQ) speed and stair climbing scores
timeFrame: Baseline to four-month follow-up
measure: Four-month change in Short-Form 36 Physical Function questionnaire score
timeFrame: Baseline to four-month follow-up
measure: Four-month change in short physical performance battery (SPPB) score
timeFrame: Baseline to four-month follow-up
measure: Four-month change in nitrate and nitrite abundance in muscle
timeFrame: Baseline to four-month follow-up
measure: Four-month change in mitochondrial oxygen consumption
timeFrame: Baseline to four-month follow-up
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
References: