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SMART Exercise for PAD (SMART PAD)

Primary Purpose

Peripheral Arterial Disease, Aging, Peripheral Vascular Diseases

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Supervised Treadmill Exercise
Home-Based Exercise
Nitrate-rich beetroot Juice
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Arterial Disease focused on measuring behavior change, patient reported outcome measure

Eligibility Criteria

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

Inclusion Criteria: First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as either: An ABI <= 0.90 at baseline. Vascular lab evidence of PAD (such as a toe brachial pressure less than or equal to 0.70 or an ankle brachial index less than or equal to 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 Limb-threatening 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 condition other than PAD Current foot ulcer on bottom of foot Unwilling to drink beetroot juice Unwilling to accept randomization into either group (home based exercise or supervised exercise) Planning to engage in new walking exercise outside of the study or unwilling to refrain from new walking exercise activity during the trial. Already exercising at a level consistent with exercise intervention. End-stage kidney disease (ESKD) associated with the need for dialysis. Planned major surgery, coronary or leg revascularization during the next six 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 or dementia. However, if the MMSE is < 23 and the Principal Investigator evaluation determines that the lower score is related to language barriers or education level, the Principal Investigator has discretion to allow a participant with MMSE < 23 to participate, as appropriate. Allergy to beetroot juice Currently consuming beetroot juice or oral nitrate or nitrite, or a beetroot supplement, and/or unwilling to avoid these during study participation. Participants currently consuming one cup of beets daily will be asked to discontinue beet ingestion 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, they will not be eligible for the clinical trial. Unstable angina Abnormal baseline stress test without subsequent clearance for exercise by physician Non-English speaking. The SMART PAD interventions are delivered by interventionists who do not speak non-English languages. The integrity of the clinical trial requires clear and effective communication for data collection and intervention delivery. The trial does not have staff members who are fluent in non-English languages, nor does it have the ability to translate all study materials into other languages. 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.] Participants in a study that involved up to three single doses of nitrate-rich beetroot juice administered on separate days may participate if a month has passed since their last dose of nitrate-rich beetroot juice. Visual impairment that limits walking ability. Baseline blood pressure <100/45. Participation in a supervised treadmill exercise program or cardiac rehabilitation program in previous three months. Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash determined to be bactericidal 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 Chicago
  • University of Minnesota
  • University of Virginia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Supervised treadmill exercise + nitrate rich beetroot juice

Supervised treadmill exercise + placebo

Home-based walking exercise + nitrate rich beetroot juice

Home-based walking exercise + placebo

Arm Description

This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks.

This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks.

This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks.

This group will be participating in Home-Based Exercise and drinking placebo beetroot juice with nitrated removed for 12 weeks.

Outcomes

Primary Outcome Measures

Six-Minute Walk Distance
Change in six-minute walk distance

Secondary Outcome Measures

Walking Impairment Questionnaire (WIQ) Distance Score
WIQ distance score - Range 0-100, 100 is best.
PROMIS Mobility Questionnaire Score
PROMIS mobility score from administered PROMIS questionnaire
20-meter Improvement in Six-Minute Walk Distance
Meaningful response to exercise interventions
Step Count
Step count measured over seven days with the FITBIT
Six-Minute Walk Distance
Change in six-minute walk distance

Full Information

First Posted
May 22, 2023
Last Updated
September 7, 2023
Sponsor
Northwestern University
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1. Study Identification

Unique Protocol Identification Number
NCT06032065
Brief Title
SMART Exercise for PAD
Acronym
SMART PAD
Official Title
Sequential Multiple Assessment Randomized Trial of Exercise for PAD: SMART Exercise for PAD (SMART PAD)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 8, 2023 (Actual)
Primary Completion Date
November 1, 2028 (Anticipated)
Study Completion Date
March 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University

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
Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. Walking exercise is first line therapy to improve walking distance for PAD, but it does not eliminate ischemic leg symptoms in most people with PAD. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. The investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. Participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
Detailed Description
Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. As of 2018, only 1.3% of patients with Medicare and symptomatic PAD had enrolled in SET. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. In 2021, the investigators reported that a home-based exercise intervention that incorporated behavioral methods significantly improved six-minute walk in PAD, compared to an attention control group. But no randomized trials have compared SET to a home-based exercise intervention that incorporated behavioral change methods in PAD. However, 45% of people with PAD do not meaningfully respond to exercise interventions, defined as failure to improve six-minute walk by > 20 meters. This phenomenon occurs for both supervised and home-based exercise. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. Therefore, the investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. In this 2 x 2 factorial design, participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Disease, Aging, Peripheral Vascular Diseases, Walking, Difficulty
Keywords
behavior change, patient reported outcome measure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Model Description
The investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. In this 2 x 2 factorial design, participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
For the beetroot juice vs. placebo comparison, this will be a double blinded study where both the participant and the people collecting data will be blinded. For the supervised exercise vs. home-based exercise comparison, the participant and investigator will not be blinded, but the outcomes assessor will be blinded.
Allocation
Randomized
Enrollment
210 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Supervised treadmill exercise + nitrate rich beetroot juice
Arm Type
Experimental
Arm Description
This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks.
Arm Title
Supervised treadmill exercise + placebo
Arm Type
Placebo Comparator
Arm Description
This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks.
Arm Title
Home-based walking exercise + nitrate rich beetroot juice
Arm Type
Experimental
Arm Description
This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks.
Arm Title
Home-based walking exercise + placebo
Arm Type
Placebo Comparator
Arm Description
This group will be participating in Home-Based Exercise and drinking placebo beetroot juice with nitrated removed for 12 weeks.
Intervention Type
Behavioral
Intervention Name(s)
Supervised Treadmill Exercise
Intervention Description
This is a 12 week intervention where participants will walk for exercise 3 times a week on a treadmill at a center while being supervised by healthcare personnel.
Intervention Type
Behavioral
Intervention Name(s)
Home-Based Exercise
Intervention Description
This is a 12 week intervention where participants will walk at home for exercise with guidance from a study coach. They will have 4 in person visits in the first four weeks and then have weekly phone calls in the last 8 weeks of the intervention with their coach.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nitrate-rich beetroot Juice
Intervention Description
Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks.
Primary Outcome Measure Information:
Title
Six-Minute Walk Distance
Description
Change in six-minute walk distance
Time Frame
Measured at baseline and 12 week follow-up
Secondary Outcome Measure Information:
Title
Walking Impairment Questionnaire (WIQ) Distance Score
Description
WIQ distance score - Range 0-100, 100 is best.
Time Frame
measured at baseline and 12 weeks
Title
PROMIS Mobility Questionnaire Score
Description
PROMIS mobility score from administered PROMIS questionnaire
Time Frame
measured at baseline and 12 weeks
Title
20-meter Improvement in Six-Minute Walk Distance
Description
Meaningful response to exercise interventions
Time Frame
measured at 12 weeks
Title
Step Count
Description
Step count measured over seven days with the FITBIT
Time Frame
measured at baseline and 12 weeks
Title
Six-Minute Walk Distance
Description
Change in six-minute walk distance
Time Frame
Measured at baseline and 24-week follow up
Other Pre-specified Outcome Measures:
Title
Physical Activity Step Count
Description
Step count measured over seven days with FITBIT
Time Frame
Measured at baseline and 24 weeks
Title
Physical activity distance
Description
Physical activity distance measured over seven days with FITBIT
Time Frame
Measured at baseline and 24 weeks.
Title
Short physical performance battery (SPPB)
Description
SPPB range, range 0-12, 12-best
Time Frame
measured at baseline and 12 weeks
Title
Walking Impairment Questionnaire (WIQ) Stair Climbing Score
Description
WIQ stair climbing score from administered WIQ, range 0-100, 100 is best.
Time Frame
measured at baseline and 12 weeks
Title
Walking Impairment Questionnaire (WIQ) Walking Speed Score
Description
WIQ walking speed score from administered WIQ, range 0-100, 100 is best
Time Frame
measured at baseline and 12 weeks
Title
Walking Impairment Questionnaire (WIQ) Stair Climbing Score
Description
WIQ stair climbing score from administered WIQ, range 0-100, 100 is best
Time Frame
measured at baseline and 24 weeks
Title
Walking Impairment Questionnaire (WIQ) Walking Speed Score
Description
WIQ walking speed score from administered WIQ, range 0-100, 100 is best
Time Frame
measured at baseline and 24 weeks
Title
Short physical performance battery (SPPB)
Description
SPPB range, range 0-12, 12-best
Time Frame
measured at baseline and 24 weeks
Title
Physical Activity Total Distance
Description
Distance walked over seven days measured with FITBIT
Time Frame
Measured at baseline and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as either: An ABI <= 0.90 at baseline. Vascular lab evidence of PAD (such as a toe brachial pressure less than or equal to 0.70 or an ankle brachial index less than or equal to 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 Limb-threatening 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 condition other than PAD Current foot ulcer on bottom of foot Unwilling to drink beetroot juice Unwilling to accept randomization into either group (home based exercise or supervised exercise) Planning to engage in new walking exercise outside of the study or unwilling to refrain from new walking exercise activity during the trial. Already exercising at a level consistent with exercise intervention. End-stage kidney disease (ESKD) associated with the need for dialysis. Planned major surgery, coronary or leg revascularization during the next six 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 or dementia. However, if the MMSE is < 23 and the Principal Investigator evaluation determines that the lower score is related to language barriers or education level, the Principal Investigator has discretion to allow a participant with MMSE < 23 to participate, as appropriate. Allergy to beetroot juice Currently consuming beetroot juice or oral nitrate or nitrite, or a beetroot supplement, and/or unwilling to avoid these during study participation. Participants currently consuming one cup of beets daily will be asked to discontinue beet ingestion 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, they will not be eligible for the clinical trial. Unstable angina Abnormal baseline stress test without subsequent clearance for exercise by physician Non-English speaking. The SMART PAD interventions are delivered by interventionists who do not speak non-English languages. The integrity of the clinical trial requires clear and effective communication for data collection and intervention delivery. The trial does not have staff members who are fluent in non-English languages, nor does it have the ability to translate all study materials into other languages. 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.] Participants in a study that involved up to three single doses of nitrate-rich beetroot juice administered on separate days may participate if a month has passed since their last dose of nitrate-rich beetroot juice. Visual impairment that limits walking ability. Baseline blood pressure <100/45. Participation in a supervised treadmill exercise program or cardiac rehabilitation program in previous three months. Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash determined to be bactericidal 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
312-503-6438
Email
mdm608@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
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tamar Polonsky, MD
Phone
773-702-6153
Email
tpolonsky@bsd.uchicago.edu
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diane Treat-Jacobson, PhD
Phone
612-624-7613
Email
treat001@umn.edu
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

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SMART Exercise for PAD

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