search
Back to results

BEETroot Juice to Reverse Functional Impairment in PAD (BEET PAD)

Primary Purpose

Peripheral Artery Disease

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Beetroot juice
Placebo
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Artery Disease focused on measuring beetroot juice, mobility, intermittent claudication, peripheral artery disease

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 <0.40 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.] Visual impairment that limits walking ability. 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. Baseline blood pressure <100/45. 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.

Sites / Locations

  • Northwestern University Feinberg School of MedicineRecruiting
  • University of ChicagoRecruiting
  • University of Virginia

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Beetroot juice

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
November 13, 2022
Last Updated
September 7, 2023
Sponsor
Northwestern University
Collaborators
University of Virginia, University of Chicago, National Institute on Aging (NIA)
search

1. Study Identification

Unique Protocol Identification Number
NCT05624125
Brief Title
BEETroot Juice to Reverse Functional Impairment in PAD
Acronym
BEET PAD
Official Title
BEETroot Juice to Reverse Functional Impairment in PAD: The BEET PAD Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 25, 2023 (Actual)
Primary Completion Date
April 1, 2028 (Anticipated)
Study Completion Date
October 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University
Collaborators
University of Virginia, University of Chicago, National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Artery Disease
Keywords
beetroot juice, mobility, intermittent claudication, peripheral artery disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
210 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Beetroot juice
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Beetroot juice
Intervention Description
Two 70 ml beetroot juice drinks daily for 4 months.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Two 70 ml placebo drinks daily for 4 months.
Primary Outcome Measure Information:
Title
Four-month change in six-minute walk distance
Description
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
Time Frame
Baseline to four-month follow-up
Secondary Outcome Measure Information:
Title
2.5 hour change in six-minute walk distance (acute effect)
Description
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
Time Frame
Baseline 2.5 hour follow-up
Title
Four-month + 24 hour change in six-minute walk distance (chronic effect)
Description
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
Time Frame
Baseline to four-month + 24 hour follow-up
Title
Four-month change in calf muscle perfusion
Description
Change in calf muscle perfusion will be compared between those randomized to beetroot juice vs. those randomized to placebo
Time Frame
Baseline to four-month follow-up
Title
Four-month change in Walking Impairment Questionnaire (WIQ) distance score
Description
Change in WIQ distance score will be compared between those randomized to beetroot juice vs. those randomized to placebo
Time Frame
Baseline to four-month follow-up
Title
Four-month change in six-minute walk distance among participants randomized to beetroot juice
Description
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
Time Frame
2.5 hour to four-month follow-up
Other Pre-specified Outcome Measures:
Title
Durability of effect on six-minute walk distance
Description
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
Time Frame
14 days after the end of the assigned study drink (intervention or placebo)
Title
Four-month change in Walking Impairment Questionnaire (WIQ) speed and stair climbing scores
Description
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
Time Frame
Baseline to four-month follow-up
Title
Four-month change in Short-Form 36 Physical Function questionnaire score
Description
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
Time Frame
Baseline to four-month follow-up
Title
Four-month change in short physical performance battery (SPPB) score
Description
Change in SPPB score at four-month follow-up will be compared between those randomized to beetroot juice vs. those randomized to placebo
Time Frame
Baseline to four-month follow-up
Title
Four-month change in nitrate and nitrite abundance in muscle
Description
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
Time Frame
Baseline to four-month follow-up
Title
Four-month change in mitochondrial oxygen consumption
Description
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
Time Frame
Baseline to four-month follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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 <0.40 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.] Visual impairment that limits walking ability. 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. Baseline blood pressure <100/45. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mary McDermott, MD
Phone
312-503-6419
Email
mdm608@northwestern.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kathryn Domanchuk, BS
Phone
312-503-6438
Email
k-domanchuk@northwestern.edu
Facility Information:
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathryn Domanchuk, BS
Phone
312-503-6438
Email
k-domanchuk@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Mary M McDermott, MD
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tamar Polonsky, MD
Phone
773-702-6153
Email
tpolonsky@bsd.uchicago.edu
First Name & Middle Initial & Last Name & Degree
Tamar Polonsky, MD
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason Allen, PhD
Phone
434-243-3508
Email
jason.allen@virginia.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

BEETroot Juice to Reverse Functional Impairment in PAD

We'll reach out to this number within 24 hrs