BEET PAD: BEETroot Juice to Reverse Functional Impairment in PAD
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Beetroot juice 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
Two 70 ml beetroot juice drinks daily for 4 months.
|
| Placebo Comparator: Placebo 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
Two 70 ml placebo drinks daily for 4 months.
|
Outcome Measures
Primary Outcome Measures
- Four-month change in six-minute walk distance [Baseline to four-month follow-up]
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
Secondary Outcome Measures
- 2.5 hour change in six-minute walk distance (acute effect) [Baseline 2.5 hour follow-up]
Change in six-minute walk distance 2.5 hours after drinking the first study beverage (acute effect) will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month + 24 hour change in six-minute walk distance (chronic effect) [Baseline to four-month + 24 hour follow-up]
Change in six-minute walk distance at four-month follow-up, 24 hours after drinking study beverage (chronic effect) will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in calf muscle perfusion [Baseline to four-month follow-up]
Change in calf muscle perfusion will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in Walking Impairment Questionnaire (WIQ) distance score [Baseline to four-month follow-up]
Change in WIQ distance score will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in six-minute walk distance among participants randomized to beetroot juice [2.5 hour to four-month follow-up]
Among those randomized to beetroot juice, investigators will determine whether those who attain a higher immediate peak or a greater increase in plasma nitrate levels at 2.5 hours after the first dose of beetroot juice at baseline will have a greater six-minute walk improvement at 4-month follow-up, compared to those with a lower peak or a smaller increase in nitrite, respectively
Other Outcome Measures
- Durability of effect on six-minute walk distance [14 days after the end of the assigned study drink (intervention or placebo)]
Change in six-minute walk distance at 14 days after the final drink that the participant was randomized to will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in Walking Impairment Questionnaire (WIQ) speed and stair climbing scores [Baseline to four-month follow-up]
Change in WIQ speed and stair climbing scores at four-month follow-up will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in Short-Form 36 Physical Function questionnaire score [Baseline to four-month follow-up]
Change in Short-Form 36 Physical Function questionnaire score at four-month follow-up will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in short physical performance battery (SPPB) score [Baseline to four-month follow-up]
Change in SPPB score at four-month follow-up will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in nitrate and nitrite abundance in muscle [Baseline to four-month follow-up]
Change in nitrate and nitrate abundance in muscle in participants who undergo gastrocnemius (calf) muscle biopsy will be compared between those randomized to beetroot juice vs. those randomized to placebo
- Four-month change in mitochondrial oxygen consumption [Baseline to four-month follow-up]
Change in mitochondrial oxygen consumption in participants who undergo gastrocnemius (calf) muscle biopsy will be compared between those randomized to beetroot juice vs. those randomized to placebo
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
Above- or below-knee amputation
-
Critical limb ischemia defined as an ABI <0.30 or <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 or oral nitrate or nitrite and/or unwilling to avoid beetroot juice during the study.
-
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.]
-
Visual impairment that limits walking ability.
-
Six-minute walk distance of <500 feet or >1600 feet.
-
Baseline blood pressure <100/50.
-
Participation in a supervised treadmill exercise program in previous three months.
-
Using an antibacterial mouthwash (such as Cepacol) or a mouthwash containing chlorhexidine and unwilling to discontinue.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northwestern University Feinberg School of Medicine | Chicago | Illinois | United States | 60611 |
| 2 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 3 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
Sponsors and Collaborators
- Northwestern University
- University of Virginia
- University of Chicago
- National Institute on Aging (NIA)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STU00217101
- R01AG073257