<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/NCT03839953</url>
  </required_header>
  <id_info>
    <org_study_id>REB17-730</org_study_id>
    <nct_id>NCT03839953</nct_id>
  </id_info>
  <brief_title>Exercise Rehabilitation for Patients With Critical Limb Ischemia After Revascularization</brief_title>
  <official_title>Exercise Rehabilitation for Critical Limb Ischemia Patients After Revascularization: Pilot Randomized Controlled Trial Assessing Functional Capacity and Quality of Life After a 12-week Rehabilitation Program Versus Best Medical Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Calgary</source>
  <oversight_info>
    <has_dmc>No</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>
      Peripheral arterial disease (PAD) affects more than 200 million people worldwide. This&#xD;
      disease occurs with narrowing and occlusion of arteries supplying oxygenated blood to the&#xD;
      organs and limbs. Symptomatic patients typically experience leg pain with physical activity.&#xD;
      More advanced disease states are referred to as critical limb ischemia (CLI), where patients&#xD;
      may have leg pain at rest or non-healing wounds. Primary treatment of PAD involves risk&#xD;
      factor management; smoking cessation, management of blood pressure, blood cholesterol,&#xD;
      diabetes, and exercise prescription. Patients with CLI typically require interventions to&#xD;
      reestablish blood supply to their limbs. There is currently minimal understanding of the role&#xD;
      for exercise rehabilitation after revascularization procedures in this vulnerable population.&#xD;
      This is the first clinical to understand the role of exercise for these patients. We&#xD;
      hypothesize that exercise rehabilitation after revascularization will improve quality of life&#xD;
      and functional capacity in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Peripheral arterial disease (PAD) refers to narrowing and occlusion of arteries&#xD;
      supplying oxygenated blood to non-coronary and non-intracranial circulatory systems. This&#xD;
      term is typically used to describe disease in the legs though it also affects upper&#xD;
      extremities, renal and mesenteric vessels. Symptomatic patients typically experience leg pain&#xD;
      with walking or physical activity which is referred to as intermittent claudication (IC). In&#xD;
      more advanced chronic disease states with severely compromised blood flow to the tissues,&#xD;
      patients may have leg pain at rest or even non healing wounds that can lead to tissue loss&#xD;
      which is defined as critical limb ischemia (CLI).&#xD;
&#xD;
      Risk factor management is critical for PAD patients with the goal of improving symptoms and&#xD;
      preventing disease progression. This includes smoking cessation as well as appropriate&#xD;
      management for hypertension, dyslipidemia and diabetes. Antiplatelet therapy should be&#xD;
      initiated in symptomatic patient or when other risk factors are present. Exercise&#xD;
      interventions should be encouraged in all patients with PAD. In patients who have progressed&#xD;
      to critical limb ischemia, treatment goals are to relieve pain, heal wounds and prevent limb&#xD;
      loss. In addition to risk factor management and medical therapy, these patients require&#xD;
      revascularization procedures. Depending on the extent and location of disease, the techniques&#xD;
      used may be endovascular/interventional (minimally invasive), surgical, or a hybrid&#xD;
      combination of the two.&#xD;
&#xD;
      There has been minimal research examining exercise rehabilitation after revascularization.&#xD;
      There are no studies that have focused on exercise rehabilitation exclusively in patients&#xD;
      with CLI.&#xD;
&#xD;
      Purpose/Objectives: The aim of this study is to develop a better understanding of the role&#xD;
      for supervised exercise rehabilitation programs (SEP) in PAD-CLI patients after&#xD;
      revascularization. This pilot study will assess the feasibility for expanding this research&#xD;
      to a larger randomized controlled trial.&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
      This is a two-phase, single-center, non-blinded randomized controlled trial.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      In phase 1, the investigators will assess feasibility. Specifically, the investigators will&#xD;
      assess rate of enrollment, barriers to participation and any methodological challenges that&#xD;
      may require changes. If phase 1 of this study shows reasonable rates of enrollment and no&#xD;
      methodological challenges, we will proceed to phase 2.&#xD;
&#xD;
      Key objectives for phase 2 are as follows:&#xD;
&#xD;
        1. The primary objective is to show how SEP affects functional capacity and quality of life&#xD;
           in patients with PAD-CLI after revascularization.&#xD;
&#xD;
        2. The secondary objective is to show how SEP affects the rate of major adverse limb events&#xD;
           (MALE) and improve survival in patients with PAD-CLI after revascularization.&#xD;
&#xD;
      Hypotheses: 1) PAD-CLI patients who have undergone revascularization will have a greater&#xD;
      improvement in functional capacity and quality of life compared with patients treated with&#xD;
      best medical therapy alone.&#xD;
&#xD;
      2) PAD-CLI patients who have undergone revascularization will have fewer MALE and improved&#xD;
      survival compared with patients treated with best medical therapy alone.&#xD;
&#xD;
      Methodology: Patients included in the study will be identified in the vascular surgery&#xD;
      outpatient clinic or through emergency department as requiring revascularization secondary to&#xD;
      critical limb ischemia. Patients will be approached regarding study participation prior to&#xD;
      the revascularization procedure. After eligibility is confirmed and patients have signed&#xD;
      informed consent, patients will be randomized to one of two groups:&#xD;
&#xD;
        1. Best Medical Therapy (BMT): Appropriate risk factor management, encouragement to&#xD;
           mobilize.&#xD;
&#xD;
        2. Supervised Exercise Program (SEP): consist of BMT plus a supervised exercise program.&#xD;
&#xD;
      Patients will undergo evaluation of functional capacity assessment using a graded treadmill&#xD;
      test at the outset of the study and after 12 weeks of either BMP or SEP. The investigators&#xD;
      will also administer a validated quality of life (QoL) questionnaire to the two different&#xD;
      groups at the outset and completion of the study. Patients will be followed annually to&#xD;
      monitor for MALE and survival.&#xD;
&#xD;
      Statistics: Normally distributed data will be presented as mean ± SD. Results at baseline and&#xD;
      12 weeks will be compared using a paired t-test. For data that is not normally distributed,&#xD;
      comparisons will be performed using a non-parametric Mann-Whitney test. Comparisons will be&#xD;
      accepted as statistically significant at 95% confidence level (p≤0.05). STATA software will&#xD;
      be used for statistical analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">February 15, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of enrollment</measure>
    <time_frame>3 months</time_frame>
    <description>A minimum of 3 patients per month should be enrolled</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Functional Capacity</measure>
    <time_frame>Three months</time_frame>
    <description>Functional capacity will be evaluated by a six-minute walk test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quality of Life assessed by VascuQuol questionnaire</measure>
    <time_frame>Three months</time_frame>
    <description>Questionnaire with 25 items validated for patients with peripheral arterial disease</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Health status assess by SF-36</measure>
    <time_frame>Three months</time_frame>
    <description>36-item self-reported survey that provides a measure of patient health</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Barriers or experiences with physical activity</measure>
    <time_frame>Three months</time_frame>
    <description>We will conduct a 30-minute interview to gain better understanding of patient experiences with exercise rehabilitation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Major adverse limb events (MALE)</measure>
    <time_frame>Five years</time_frame>
    <description>Clinical deterioration or condition requiring surgical interventions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">64</enrollment>
  <condition>Peripheral Arterial Disease</condition>
  <condition>Critical Limb Ischemia</condition>
  <arm_group>
    <arm_group_label>Best Medical Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After undergoing revascularization for critical limb ischemia, patients will receive best medical therapy under the supervision of a vascular internal medicine specialist. This care will include advice on smoking cessation, physical activity guidelines, blood pressure regulation, statin administration and possible anti-platelet administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Supervised Exercise Program</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive best medical therapy plus participation in a 12-week supervised exercise program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Supervised Exercise Program</intervention_name>
    <description>This intervention is a 12-week supervised exercise program at an established cardiac rehabilitation facility.</description>
    <arm_group_label>Supervised Exercise Program</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Best Medical Therapy</intervention_name>
    <description>After undergoing revascularization for critical limb ischemia, patients will receive best medical therapy under the supervision of a vascular internal medicine specialist. This care will include advice on smoking cessation, physical activity guidelines, blood pressure regulation, statin administration and possible anti-platelet administration.</description>
    <arm_group_label>Best Medical Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ambulating prior to procedure&#xD;
&#xD;
          2. Living independently prior to procedure&#xD;
&#xD;
          3. Available to attend all SEP and follow-up appointments&#xD;
&#xD;
          4. PAD Fontaine class III and IV (rest pain and tissue loss)&#xD;
&#xD;
          5. Entry with consent of vascular surgeon&#xD;
&#xD;
          6. Ischemia secondary to TASC A-D lesions identified on imaging (CTA or angiogram)&#xD;
&#xD;
          7. Able to understand and sign informed consent&#xD;
&#xD;
          8. &gt;18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Confined to wheelchair&#xD;
&#xD;
          2. Patients with exercise tolerance limitations due to other co-morbidities such as&#xD;
             cardiorespiratory, musculoskeletal, or peripheral neuropathy. (NYHA class III and IV)&#xD;
&#xD;
          3. PAD Fontaine class I and II (asymptomatic, claudication)&#xD;
&#xD;
          4. Patients with ongoing tissue loss that limits ambulation&#xD;
&#xD;
          5. Patient with previous revascularization procedures&#xD;
&#xD;
          6. Patients undergoing revascularization for acute limb ischemia events&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Randy D Moore, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peter Lougheed Center, Alberta Health Services, University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T1Y 6J4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>May 23, 2019</last_update_submitted>
  <last_update_submitted_qc>May 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Randy Moore</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Rehabilitation</keyword>
  <keyword>Exercise</keyword>
  <keyword>Revascularization</keyword>
  <keyword>Endovascular</keyword>
  <keyword>Vascular Surgery</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>Chronic Limb-Threatening Ischemia</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 19, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03839953/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03839953/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03839953
org study id: REB17-730
nct id: NCT03839953
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Peripheral arterial disease (PAD) affects more than 200 million people worldwide. This
      disease occurs with narrowing and occlusion of arteries supplying oxygenated blood to the
      organs and limbs. Symptomatic patients typically experience leg pain with physical activity.
      More advanced disease states are referred to as critical limb ischemia (CLI), where patients
      may have leg pain at rest or non-healing wounds. Primary treatment of PAD involves risk
      factor management; smoking cessation, management of blood pressure, blood cholesterol,
      diabetes, and exercise prescription. Patients with CLI typically require interventions to
      reestablish blood supply to their limbs. There is currently minimal understanding of the role
      for exercise rehabilitation after revascularization procedures in this vulnerable population.
      This is the first clinical to understand the role of exercise for these patients. We
      hypothesize that exercise rehabilitation after revascularization will improve quality of life
      and functional capacity in these patients.
Background: Peripheral arterial disease (PAD) refers to narrowing and occlusion of arteries
      supplying oxygenated blood to non-coronary and non-intracranial circulatory systems. This
      term is typically used to describe disease in the legs though it also affects upper
      extremities, renal and mesenteric vessels. Symptomatic patients typically experience leg pain
      with walking or physical activity which is referred to as intermittent claudication (IC). In
      more advanced chronic disease states with severely compromised blood flow to the tissues,
      patients may have leg pain at rest or even non healing wounds that can lead to tissue loss
      which is defined as critical limb ischemia (CLI).

      Risk factor management is critical for PAD patients with the goal of improving symptoms and
      preventing disease progression. This includes smoking cessation as well as appropriate
      management for hypertension, dyslipidemia and diabetes. Antiplatelet therapy should be
      initiated in symptomatic patient or when other risk factors are present. Exercise
      interventions should be encouraged in all patients with PAD. In patients who have progressed
      to critical limb ischemia, treatment goals are to relieve pain, heal wounds and prevent limb
      loss. In addition to risk factor management and medical therapy, these patients require
      revascularization procedures. Depending on the extent and location of disease, the techniques
      used may be endovascular/interventional (minimally invasive), surgical, or a hybrid
      combination of the two.

      There has been minimal research examining exercise rehabilitation after revascularization.
      There are no studies that have focused on exercise rehabilitation exclusively in patients
      with CLI.

      Purpose/Objectives: The aim of this study is to develop a better understanding of the role
      for supervised exercise rehabilitation programs (SEP) in PAD-CLI patients after
      revascularization. This pilot study will assess the feasibility for expanding this research
      to a larger randomized controlled trial.

      Study Design:

      This is a two-phase, single-center, non-blinded randomized controlled trial.

      Objectives:

      In phase 1, the investigators will assess feasibility. Specifically, the investigators will
      assess rate of enrollment, barriers to participation and any methodological challenges that
      may require changes. If phase 1 of this study shows reasonable rates of enrollment and no
      methodological challenges, we will proceed to phase 2.

      Key objectives for phase 2 are as follows:

        1. The primary objective is to show how SEP affects functional capacity and quality of life
           in patients with PAD-CLI after revascularization.

        2. The secondary objective is to show how SEP affects the rate of major adverse limb events
           (MALE) and improve survival in patients with PAD-CLI after revascularization.

      Hypotheses: 1) PAD-CLI patients who have undergone revascularization will have a greater
      improvement in functional capacity and quality of life compared with patients treated with
      best medical therapy alone.

      2) PAD-CLI patients who have undergone revascularization will have fewer MALE and improved
      survival compared with patients treated with best medical therapy alone.

      Methodology: Patients included in the study will be identified in the vascular surgery
      outpatient clinic or through emergency department as requiring revascularization secondary to
      critical limb ischemia. Patients will be approached regarding study participation prior to
      the revascularization procedure. After eligibility is confirmed and patients have signed
      informed consent, patients will be randomized to one of two groups:

        1. Best Medical Therapy (BMT): Appropriate risk factor management, encouragement to
           mobilize.

        2. Supervised Exercise Program (SEP): consist of BMT plus a supervised exercise program.

      Patients will undergo evaluation of functional capacity assessment using a graded treadmill
      test at the outset of the study and after 12 weeks of either BMP or SEP. The investigators
      will also administer a validated quality of life (QoL) questionnaire to the two different
      groups at the outset and completion of the study. Patients will be followed annually to
      monitor for MALE and survival.

      Statistics: Normally distributed data will be presented as mean ± SD. Results at baseline and
      12 weeks will be compared using a paired t-test. For data that is not normally distributed,
      comparisons will be performed using a non-parametric Mann-Whitney test. Comparisons will be
      accepted as statistically significant at 95% confidence level (p≤0.05). STATA software will
      be used for statistical analysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of enrollment
time frame: 3 months
description: A minimum of 3 patients per month should be enrolled
measure: Functional Capacity
time frame: Three months
description: Functional capacity will be evaluated by a six-minute walk test
measure: Quality of Life assessed by VascuQuol questionnaire
time frame: Three months
description: Questionnaire with 25 items validated for patients with peripheral arterial disease
measure: Health status assess by SF-36
time frame: Three months
description: 36-item self-reported survey that provides a measure of patient health
measure: Barriers or experiences with physical activity
time frame: Three months
description: We will conduct a 30-minute interview to gain better understanding of patient experiences with exercise rehabilitation.
measure: Major adverse limb events (MALE)
time frame: Five years
description: Clinical deterioration or condition requiring surgical interventions
arm group label: Best Medical Therapy
arm group type: Active Comparator
description: After undergoing revascularization for critical limb ischemia, patients will receive best medical therapy under the supervision of a vascular internal medicine specialist. This care will include advice on smoking cessation, physical activity guidelines, blood pressure regulation, statin administration and possible anti-platelet administration.
arm group label: Supervised Exercise Program
arm group type: Experimental
description: Patients will receive best medical therapy plus participation in a 12-week supervised exercise program.
intervention type: Behavioral
intervention name: Supervised Exercise Program
description: This intervention is a 12-week supervised exercise program at an established cardiac rehabilitation facility.
arm group label: Supervised Exercise Program
intervention type: Other
intervention name: Best Medical Therapy
description: After undergoing revascularization for critical limb ischemia, patients will receive best medical therapy under the supervision of a vascular internal medicine specialist. This care will include advice on smoking cessation, physical activity guidelines, blood pressure regulation, statin administration and possible anti-platelet administration.
arm group label: Best Medical Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Randy D Moore, MD
role: Principal Investigator
affiliation: University of Calgary
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Randy Moore
investigator title: Principal Investigator
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
mesh term: Chronic Limb-Threatening Ischemia
mesh term: Ischemia
sharing ipd: No
provided document: 
provided document: 