xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06032065</url>
    </required_header>
    <id_info>
      <org_study_id>STU00218112</org_study_id>
      <nct_id>NCT06032065</nct_id>
    </id_info>
    <brief_title>SMART Exercise for PAD</brief_title>
    <acronym>SMART PAD</acronym>
    <official_title>Sequential Multiple Assessment Randomized Trial of Exercise for PAD: SMART Exercise for PAD (SMART PAD)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Northwestern University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Northwestern University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times&#xD;
        weekly at a center while supervised by healthcare personnel, is first line therapy for people&#xD;
        disabled by lower extremity peripheral artery disease (PAD). However, travelling three&#xD;
        times/week to a center for SET is burdensome. Compared to SET, home-based exercise is more&#xD;
        accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based&#xD;
        exercise for PAD. Walking exercise is first line therapy to improve walking distance for PAD,&#xD;
        but it does not eliminate ischemic leg symptoms in most people with PAD. The investigators'&#xD;
        work and that of others showed that nitrate-rich beetroot juice, which increases plasma&#xD;
        nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise&#xD;
        tolerance and reduced non-response to exercise in people with and without PAD. The&#xD;
        investigators will use a 2 x 2 factorial design to address two major barriers to achieving&#xD;
        benefits from exercise therapy for PAD: First, guideline recommendations for supervised&#xD;
        exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise&#xD;
        therapy to eliminate PAD-related disability in most people with PAD. Participants will be&#xD;
        randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich&#xD;
        beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise +&#xD;
        nitrate rich beetroot juice, home-based walking exercise + placebo.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times&#xD;
        weekly at a center while supervised by healthcare personnel, is first line therapy for people&#xD;
        disabled by lower extremity peripheral artery disease (PAD). However, travelling three&#xD;
        times/week to a center for SET is burdensome. As of 2018, only 1.3% of patients with Medicare&#xD;
        and symptomatic PAD had enrolled in SET. Compared to SET, home-based exercise is more&#xD;
        accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based&#xD;
        exercise for PAD. In 2021, the investigators reported that a home-based exercise intervention&#xD;
        that incorporated behavioral methods significantly improved six-minute walk in PAD, compared&#xD;
        to an attention control group. But no randomized trials have compared SET to a home-based&#xD;
        exercise intervention that incorporated behavioral change methods in PAD. However, 45% of&#xD;
        people with PAD do not meaningfully respond to exercise interventions, defined as failure to&#xD;
        improve six-minute walk by &gt; 20 meters. This phenomenon occurs for both supervised and&#xD;
        home-based exercise. The investigators' work and that of others showed that nitrate-rich&#xD;
        beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function,&#xD;
        significantly improved exercise tolerance and reduced non-response to exercise in people with&#xD;
        and without PAD. Therefore, the investigators will use a 2 x 2 factorial design to address&#xD;
        two major barriers to achieving benefits from exercise therapy for PAD: First, guideline&#xD;
        recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second,&#xD;
        the inability of exercise therapy to eliminate PAD-related disability in most people with&#xD;
        PAD. In this 2 x 2 factorial design, participants will be randomized to one of four groups&#xD;
        for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised&#xD;
        treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice,&#xD;
        home-based walking exercise + placebo.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 8, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2029</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2028</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Factorial Assignment</intervention_model>
      <intervention_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.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <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.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Six-Minute Walk Distance</measure>
      <time_frame>Measured at baseline and 12 week follow-up</time_frame>
      <description>Change in six-minute walk distance</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Walking Impairment Questionnaire (WIQ) Distance Score</measure>
      <time_frame>measured at baseline and 12 weeks</time_frame>
      <description>WIQ distance score - Range 0-100, 100 is best.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PROMIS Mobility Questionnaire Score</measure>
      <time_frame>measured at baseline and 12 weeks</time_frame>
      <description>PROMIS mobility score from administered PROMIS questionnaire</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>20-meter Improvement in Six-Minute Walk Distance</measure>
      <time_frame>measured at 12 weeks</time_frame>
      <description>Meaningful response to exercise interventions</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Step Count</measure>
      <time_frame>measured at baseline and 12 weeks</time_frame>
      <description>Step count measured over seven days with the FITBIT</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Six-Minute Walk Distance</measure>
      <time_frame>Measured at baseline and 24-week follow up</time_frame>
      <description>Change in six-minute walk distance</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Physical Activity Step Count</measure>
      <time_frame>Measured at baseline and 24 weeks</time_frame>
      <description>Step count measured over seven days with FITBIT</description>
    </other_outcome>
    <other_outcome>
      <measure>Physical activity distance</measure>
      <time_frame>Measured at baseline and 24 weeks.</time_frame>
      <description>Physical activity distance measured over seven days with FITBIT</description>
    </other_outcome>
    <other_outcome>
      <measure>Short physical performance battery (SPPB)</measure>
      <time_frame>measured at baseline and 12 weeks</time_frame>
      <description>SPPB range, range 0-12, 12-best</description>
    </other_outcome>
    <other_outcome>
      <measure>Walking Impairment Questionnaire (WIQ) Stair Climbing Score</measure>
      <time_frame>measured at baseline and 12 weeks</time_frame>
      <description>WIQ stair climbing score from administered WIQ, range 0-100, 100 is best.</description>
    </other_outcome>
    <other_outcome>
      <measure>Walking Impairment Questionnaire (WIQ) Walking Speed Score</measure>
      <time_frame>measured at baseline and 12 weeks</time_frame>
      <description>WIQ walking speed score from administered WIQ, range 0-100, 100 is best</description>
    </other_outcome>
    <other_outcome>
      <measure>Walking Impairment Questionnaire (WIQ) Stair Climbing Score</measure>
      <time_frame>measured at baseline and 24 weeks</time_frame>
      <description>WIQ stair climbing score from administered WIQ, range 0-100, 100 is best</description>
    </other_outcome>
    <other_outcome>
      <measure>Walking Impairment Questionnaire (WIQ) Walking Speed Score</measure>
      <time_frame>measured at baseline and 24 weeks</time_frame>
      <description>WIQ walking speed score from administered WIQ, range 0-100, 100 is best</description>
    </other_outcome>
    <other_outcome>
      <measure>Short physical performance battery (SPPB)</measure>
      <time_frame>measured at baseline and 24 weeks</time_frame>
      <description>SPPB range, range 0-12, 12-best</description>
    </other_outcome>
    <other_outcome>
      <measure>Physical Activity Total Distance</measure>
      <time_frame>Measured at baseline and 12 weeks</time_frame>
      <description>Distance walked over seven days measured with FITBIT</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">210</enrollment>
    <condition>Peripheral Arterial Disease</condition>
    <condition>Aging</condition>
    <condition>Peripheral Vascular Diseases</condition>
    <condition>Walking, Difficulty</condition>
    <arm_group>
      <arm_group_label>Supervised treadmill exercise + nitrate rich beetroot juice</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Supervised treadmill exercise + placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Home-based walking exercise + nitrate rich beetroot juice</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Home-based walking exercise + placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>This group will be participating in Home-Based Exercise and drinking placebo beetroot juice with nitrated removed for 12 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Supervised Treadmill Exercise</intervention_name>
      <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.</description>
      <arm_group_label>Supervised treadmill exercise + nitrate rich beetroot juice</arm_group_label>
      <arm_group_label>Supervised treadmill exercise + placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Home-Based Exercise</intervention_name>
      <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.</description>
      <arm_group_label>Home-based walking exercise + nitrate rich beetroot juice</arm_group_label>
      <arm_group_label>Home-based walking exercise + placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Nitrate-rich beetroot Juice</intervention_name>
      <description>Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks.</description>
      <arm_group_label>Home-based walking exercise + nitrate rich beetroot juice</arm_group_label>
      <arm_group_label>Supervised treadmill exercise + nitrate rich beetroot juice</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          First, all participants will be age 50 and older. Second, all participants will have PAD.&#xD;
          PAD will be defined as either:&#xD;
  &#xD;
            1. An ABI &lt;= 0.90 at baseline.&#xD;
  &#xD;
            2. Vascular lab evidence of PAD (such as a toe brachial pressure less than or equal to&#xD;
               0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence&#xD;
               of PAD defined as at least 70% stenosis of an artery supplying the lower extremities.&#xD;
  &#xD;
            3. An ABI of &gt;0.90 and &lt;1.00 who experience a 20% or greater drop in ABI in either leg&#xD;
               after the heel-rise test.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Above- or below-knee amputation&#xD;
  &#xD;
            2. Limb-threatening ischemia defined as an ABI &lt;0.40 with symptoms of rest pain&#xD;
  &#xD;
            3. Wheelchair confinement or requiring a walker to ambulate&#xD;
  &#xD;
            4. Walking is limited by a condition other than PAD&#xD;
  &#xD;
            5. Current foot ulcer on bottom of foot&#xD;
  &#xD;
            6. Unwilling to drink beetroot juice&#xD;
  &#xD;
            7. Unwilling to accept randomization into either group (home based exercise or supervised&#xD;
               exercise)&#xD;
  &#xD;
            8. Planning to engage in new walking exercise outside of the study or unwilling to&#xD;
               refrain from new walking exercise activity during the trial.&#xD;
  &#xD;
            9. Already exercising at a level consistent with exercise intervention.&#xD;
  &#xD;
           10. End-stage kidney disease (ESKD) associated with the need for dialysis.&#xD;
  &#xD;
           11. Planned major surgery, coronary or leg revascularization during the next six months&#xD;
  &#xD;
           12. Major surgery, coronary or leg revascularization or major cardiovascular event in the&#xD;
               previous three months&#xD;
  &#xD;
           13. Major medical illness including lung disease requiring oxygen, Parkinson's disease, a&#xD;
               life-threatening illness with life expectancy less than six months, or cancer&#xD;
               requiring treatment in the previous two years. [NOTE: potential participants may still&#xD;
               qualify if they have had treatment for an early stage cancer in the past two years and&#xD;
               the prognosis is excellent. Participants who require oxygen only at night may still&#xD;
               qualify.]&#xD;
  &#xD;
           14. Mini-Mental Status Examination (MMSE) score &lt; 23 or dementia. However, if the MMSE is&#xD;
               &lt; 23 and the Principal Investigator evaluation determines that the lower score is&#xD;
               related to language barriers or education level, the Principal Investigator has&#xD;
               discretion to allow a participant with MMSE &lt; 23 to participate, as appropriate.&#xD;
  &#xD;
           15. Allergy to beetroot juice&#xD;
  &#xD;
           16. Currently consuming beetroot juice or oral nitrate or nitrite, or a beetroot&#xD;
               supplement, and/or unwilling to avoid these during study participation. Participants&#xD;
               currently consuming one cup of beets daily will be asked to discontinue beet ingestion&#xD;
               for 30 days before baseline testing and throughout the clinical trial. If the&#xD;
               potential participant is unwilling to refrain from daily beet consumption of one cup&#xD;
               or more, they will not be eligible for the clinical trial.&#xD;
  &#xD;
           17. Unstable angina&#xD;
  &#xD;
           18. Abnormal baseline stress test without subsequent clearance for exercise by physician&#xD;
  &#xD;
           19. Non-English speaking. The SMART PAD interventions are delivered by interventionists&#xD;
               who do not speak non-English languages. The integrity of the clinical trial requires&#xD;
               clear and effective communication for data collection and intervention delivery. The&#xD;
               trial does not have staff members who are fluent in non-English languages, nor does it&#xD;
               have the ability to translate all study materials into other languages.&#xD;
  &#xD;
           20. Participation in or completion of a clinical trial in the previous three months.&#xD;
               [NOTE: after completing a stem cell or gene therapy intervention, participants will&#xD;
               become eligible after the final study follow-up visit of the stem cell or gene therapy&#xD;
               study so long as at least six months have passed since the final intervention&#xD;
               administration. After completing a supplement or drug therapy (other than stem cell or&#xD;
               gene therapy), participants will be eligible after the final study follow-up visit as&#xD;
               long as at least three months have passed since the final intervention of the trial.]&#xD;
               Participants in a study that involved up to three single doses of nitrate-rich&#xD;
               beetroot juice administered on separate days may participate if a month has passed&#xD;
               since their last dose of nitrate-rich beetroot juice.&#xD;
  &#xD;
           21. Visual impairment that limits walking ability.&#xD;
  &#xD;
           22. Baseline blood pressure &lt;100/45.&#xD;
  &#xD;
           23. Participation in a supervised treadmill exercise program or cardiac rehabilitation&#xD;
               program in previous three months.&#xD;
  &#xD;
           24. Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash&#xD;
               determined to be bactericidal and unwilling to discontinue.&#xD;
  &#xD;
           25. In addition to the above criteria, investigator discretion will be used to determine&#xD;
               if the trial is unsafe or not a good fit for the potential participant.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Mary McDermott, MD</last_name>
      <phone>312-503-6438</phone>
      <email>mdm608@northwestern.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Northwestern University Feinberg School of Medicine</name>
        <address>
          <city>Chicago</city>
          <state>Illinois</state>
          <zip>60611</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Kathryn Domanchuk, BS</last_name>
        <phone>312-503-6438</phone>
        <email>k-domanchuk@northwestern.edu</email>
      </contact>
      <investigator>
        <last_name>Mary M McDermott, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Chicago</name>
        <address>
          <city>Chicago</city>
          <state>Illinois</state>
          <zip>60637</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Tamar Polonsky, MD</last_name>
        <phone>773-702-6153</phone>
        <email>tpolonsky@bsd.uchicago.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University of Minnesota</name>
        <address>
          <city>Minneapolis</city>
          <state>Minnesota</state>
          <zip>55455</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Diane Treat-Jacobson, PhD</last_name>
        <phone>612-624-7613</phone>
        <email>treat001@umn.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University of Virginia</name>
        <address>
          <city>Charlottesville</city>
          <state>Virginia</state>
          <zip>22903</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Jason Allen, PhD</last_name>
        <phone>434-243-3508</phone>
        <email>jason.allen@virginia.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>May 22, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Northwestern University</investigator_affiliation>
      <investigator_full_name>Mary McDermott</investigator_full_name>
      <investigator_title>Jeremiah Stamler Professor of Medicine</investigator_title>
    </responsible_party>
    <keyword>behavior change</keyword>
    <keyword>patient reported outcome measure</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peripheral Arterial Disease</mesh_term>
      <mesh_term>Peripheral Vascular Diseases</mesh_term>
      <mesh_term>Vascular Diseases</mesh_term>
      <mesh_term>Mobility Limitation</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06032065
  org study id: STU00218112
  nct id: NCT06032065
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Factorial Assignment
  intervention 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.
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
  measure: Six-Minute Walk Distance
  time frame: Measured at baseline and 12 week follow-up
  description: Change in six-minute walk distance
  measure: Walking Impairment Questionnaire (WIQ) Distance Score
  time frame: measured at baseline and 12 weeks
  description: WIQ distance score - Range 0-100, 100 is best.
  measure: PROMIS Mobility Questionnaire Score
  time frame: measured at baseline and 12 weeks
  description: PROMIS mobility score from administered PROMIS questionnaire
  measure: 20-meter Improvement in Six-Minute Walk Distance
  time frame: measured at 12 weeks
  description: Meaningful response to exercise interventions
  measure: Step Count
  time frame: measured at baseline and 12 weeks
  description: Step count measured over seven days with the FITBIT
  measure: Six-Minute Walk Distance
  time frame: Measured at baseline and 24-week follow up
  description: Change in six-minute walk distance
  measure: Physical Activity Step Count
  time frame: Measured at baseline and 24 weeks
  description: Step count measured over seven days with FITBIT
  measure: Physical activity distance
  time frame: Measured at baseline and 24 weeks.
  description: Physical activity distance measured over seven days with FITBIT
  measure: Short physical performance battery (SPPB)
  time frame: measured at baseline and 12 weeks
  description: SPPB range, range 0-12, 12-best
  measure: Walking Impairment Questionnaire (WIQ) Stair Climbing Score
  time frame: measured at baseline and 12 weeks
  description: WIQ stair climbing score from administered WIQ, range 0-100, 100 is best.
  measure: Walking Impairment Questionnaire (WIQ) Walking Speed Score
  time frame: measured at baseline and 12 weeks
  description: WIQ walking speed score from administered WIQ, range 0-100, 100 is best
  measure: Walking Impairment Questionnaire (WIQ) Stair Climbing Score
  time frame: measured at baseline and 24 weeks
  description: WIQ stair climbing score from administered WIQ, range 0-100, 100 is best
  measure: Walking Impairment Questionnaire (WIQ) Walking Speed Score
  time frame: measured at baseline and 24 weeks
  description: WIQ walking speed score from administered WIQ, range 0-100, 100 is best
  measure: Short physical performance battery (SPPB)
  time frame: measured at baseline and 24 weeks
  description: SPPB range, range 0-12, 12-best
  measure: Physical Activity Total Distance
  time frame: Measured at baseline and 12 weeks
  description: Distance walked over seven days measured with FITBIT
  arm group label: Supervised treadmill exercise + nitrate rich beetroot juice
  arm group type: Experimental
  description: This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks.
  arm group label: Supervised treadmill exercise + placebo
  arm group type: Placebo Comparator
  description: This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks.
  arm group label: Home-based walking exercise + nitrate rich beetroot juice
  arm group type: Experimental
  description: This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks.
  arm group label: Home-based walking exercise + placebo
  arm group type: Placebo Comparator
  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: Supervised Treadmill Exercise
  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.
  arm group label: Supervised treadmill exercise + nitrate rich beetroot juice
  arm group label: Supervised treadmill exercise + placebo
  intervention type: Behavioral
  intervention name: Home-Based Exercise
  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.
  arm group label: Home-based walking exercise + nitrate rich beetroot juice
  arm group label: Home-based walking exercise + placebo
  intervention type: Dietary Supplement
  intervention name: Nitrate-rich beetroot Juice
  description: Participants will drink one shot of nitrate rich beet-root juice twice daily for 12 weeks.
  arm group label: Home-based walking exercise + nitrate rich beetroot juice
  arm group label: Supervised treadmill exercise + nitrate rich beetroot juice
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Mary McDermott, MD
  phone: 312-503-6438
  email: mdm608@northwestern.edu
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Northwestern University
  investigator full name: Mary McDermott
  investigator title: Jeremiah Stamler Professor of Medicine
  mesh term: Peripheral Arterial Disease
  mesh term: Peripheral Vascular Diseases
  mesh term: Vascular Diseases
  mesh term: Mobility Limitation