<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/NCT02210845</url>
  </required_header>
  <id_info>
    <org_study_id>DOS-23</org_study_id>
    <nct_id>NCT02210845</nct_id>
  </id_info>
  <brief_title>Lifestyle Strategies for Improving Diabetes Outcomes</brief_title>
  <official_title>Impact of Two Lifestyle Strategies for Improving Diabetes Related Health Outcomes in a Specialty Care Setting: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tom Elliott</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BCDiabetes.Ca</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>
      The objective of this study is to investigate whether a behavioral modification intervention&#xD;
      in the form of either a 6-month supervised training program or a 6-month financial incentive&#xD;
      weight loss program, results in improvement of diabetes outcome such as overall sugar control&#xD;
      and lipid control.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, prospective, unblinded, randomized, controlled, clinical trial of&#xD;
      200 subjects randomized to either a Supervised Training Program (STP), Incentivized Weight&#xD;
      Loss (IWL) or Standard of Care (SoC).&#xD;
&#xD;
      Subjects randomized to the SoC group will be asked to return for regular 3-monthly clinic&#xD;
      visits and for diet and exercise recommendations.The STP group will be offered once-weekly&#xD;
      one hour supervised training sessions at no charge for a period of six months in the&#xD;
      bcdiabetes.ca fitness center (located in the Vancouver General Hospital Employee Centre gym).&#xD;
&#xD;
      The IWL group will receive a financial reward for achieving monthly weight loss targets.&#xD;
      Those who fail to meet their monthly goals will receive no financial reward. Such financial&#xD;
      incentives have been considered in previous research. Due to the nature of the intervention,&#xD;
      none of the investigative staff, trainers or subjects will be blinded to randomized&#xD;
      assignment.&#xD;
&#xD;
      The primary objective of this study is to investigate whether a behavioral modification&#xD;
      intervention in the form of either a 6-month supervised training program or a 6-month&#xD;
      financial incentive program, results in overall superior clinical outcomes in comparison to&#xD;
      standard of care. Specifically, improvement in glucose control, measured by A1c, will be&#xD;
      considered. Given the objective nature of the Primary Outcome, there is little possibility of&#xD;
      assessment bias of the primary or clinical outcomes.The secondary objective is to investigate&#xD;
      the impact of a supervised training program and an incentivized weight loss program on&#xD;
      weight-loss, LDL (apoB), blood pressure, waist-hip circumference, and diabetes-specific&#xD;
      quality of life measures including behavioral and emotional impact (refer to Secondary&#xD;
      Outcomes section).&#xD;
&#xD;
      Patients attending BCDiabetes ( Diabetes Clinic at Diamond Center )will be approached by one&#xD;
      of their diabetes caregivers who will describe the study and determine whether they have&#xD;
      interest in participating. If the patient expresses an interest, they will be provided&#xD;
      additional information and a study consent form and be free to ask questions about the study.&#xD;
      They may choose to provide consent at the time or to leave with the consent form and return&#xD;
      at a later time to ask further questions. A research nurse, coordinator and/or co/principal&#xD;
      investigator will be available to answer any questions the patient may have. When consent is&#xD;
      provided, confirmation of the eligibility criteria will be completed and the subject will&#xD;
      receive their randomized group assignment.&#xD;
&#xD;
      Eligible subjects will be randomized in a 2:1:1 fashion to the SoC, STP and IWL and groups&#xD;
      respectively. Randomization will be stratified by age (≤ 50 vs &gt; 50 years of age) to ensure&#xD;
      balance in age groups in all three treatment arms; enrollment will not be stratified and the&#xD;
      number of participants in the two age groups will not be restricted. Randomization within&#xD;
      strata will be done in a permuted complete block design with random block sizes (blocks no&#xD;
      smaller than 6 and no larger than 15). Randomization will be completed in advance and&#xD;
      assignments will be kept in individual, separate sealed, sequentially labeled envelopes&#xD;
      opened at the time of randomization of each individual.&#xD;
&#xD;
      Withdrawal from Study or Intervention:&#xD;
&#xD;
      Although they should be encouraged to continue participation in their randomized group,&#xD;
      subjects can choose to withdraw from the study, or to withdraw from the intervention at any&#xD;
      time. Subjects who choose to withdraw from the STP and IWL arms should continue to receive&#xD;
      standard of care and will be considered cross-overs to SoC arm; these subjects are not&#xD;
      necessarily withdrawing from the study and should be encouraged to continue to return for&#xD;
      their scheduled 3 and 6 month study visits so study outcomes can be measured. If a subject&#xD;
      chooses to withdraw from the study entirely, all attempts should be made to have them&#xD;
      complete an exit visit where all study outcomes can be captured.&#xD;
&#xD;
      Subjects who experience any adverse event related to the STP arm (eg: physical injury while&#xD;
      training) or experience the onset or worsening of an signs or symptoms related to a medical&#xD;
      condition (eg: shortness of breath, dizziness, vomiting nausea, etc) persisting the day&#xD;
      following a supervised training session, or who experience a worsening of a physical&#xD;
      condition (eg: degenerative disc disorder, knee or hip pain, plantar fasciitis, etc) will be&#xD;
      withdrawn from the STP intervention. As above, these subjects will be asked to return for&#xD;
      their scheduled 3 and 6 month clinic visits.&#xD;
&#xD;
      If at any point more than 15% of subjects in the STP arm are withdrawn from the intervention&#xD;
      arm due to an adverse event, worsening medical or physical condition, the study will be&#xD;
      stopped.&#xD;
&#xD;
      Study data will be collected as part of the subject's electronic medical record at&#xD;
      bcdiabetes.ca. Identifiable study data will be housed exclusively on bcdiabetes.ca; if&#xD;
      removed from bcdiabetes.ca servers, subjects will be identified only with a study&#xD;
      registration number different from their BC CareID number. Remote monitoring by EMMES using&#xD;
      confidential authenticated automatically scheduled direct database queries. EMMES Canada will&#xD;
      also provide oversight of quality assurance &amp; monitoring.&#xD;
&#xD;
      The primary outcome measure is the percent of subjects who achieve target for A1c. The null&#xD;
      and research hypothesis supporting the primary objective of investigating the impact of&#xD;
      whether a behavioral modification intervention in the form of either a 6-month supervised&#xD;
      training program or a 6-month incentivized weight loss program, results in overall superior&#xD;
      clinical outcomes in comparison to standard of care is then:&#xD;
&#xD;
      H0: pSoC ≥ pIWL and pSoC ≥ pSTP vs. H1: pSoC &lt; pIWL or pSoC &lt; pSTP&#xD;
&#xD;
      where pSoC , pSTP and pIWL are the proportion of subjects achieving the target for all three&#xD;
      disease measures. Here, rejecting the null hypothesis implies that the percent of patients&#xD;
      achieving targets is higher in either of the STP arm or the IWL arm than in the SoC arm. A&#xD;
      one-sided, 0.05 alpha-level simultaneous test for multiple contrasts of binomial proportions&#xD;
      with an &quot;Add-2&quot; adjustment will be used.&#xD;
&#xD;
      The primary analysis cohort will be an ITT cohort including all randomized subjects and&#xD;
      considering the arm to which they were originally randomized regardless of adherence to the&#xD;
      regimen or the study protocol. Subjects who cross-over to the other intervention prior to&#xD;
      Month 3 (ie: complete less than 3 of the required 6 months) will be considered failures in&#xD;
      the arm to which they were originally randomized. Clinical data from the last, or exit visit&#xD;
      will be used to construct the primary outcome for subjects who withdraw from the study, or&#xD;
      from the intervention, subsequent to Month 3.&#xD;
&#xD;
      To corroborate the primary, unadjusted analysis, a logistic regression model will be fit with&#xD;
      baseline clinical and demographic data as well as measures of compliance to intervention to&#xD;
      adjust for possible imbalance of important variables. Also, the primary analysis will be&#xD;
      repeated on a per-protocol cohort of subjects who completed the study according to the&#xD;
      protocol and did not cross-over or withdraw from therapy. Graphical techniques and summary&#xD;
      statistics for the two randomized groups at baseline and months 3 and 6 will also be&#xD;
      presented.&#xD;
&#xD;
      Summary statistics and graphical presentations will be used to summarize data for all&#xD;
      secondary outcomes. All hypothesis tests will be 2-sided and with a 5% Type I error&#xD;
      probability. There will be no adjustment for multiple comparisons among the secondary&#xD;
      outcomes with the exception that multiple domains within a single psychosocial instrument&#xD;
      (eg: emotional burden, physician-related distress, regimen-related distress, and&#xD;
      diabetes-related interpersonal distress domains within the DDS) will be subject to a&#xD;
      Benjamini-Hochberg multiple comparison adjustment. Analyses will be conducted on the ITT&#xD;
      cohort and corroborated by analysis on the per-protocol cohort.&#xD;
&#xD;
      Each clinical outcome measure is captured as a continuous and dichotomized variable (eg: A1c&#xD;
      absolute level and those &lt; 7.0%). Dichotomized variables will be analyzed as described in the&#xD;
      Primary Analysis.&#xD;
&#xD;
      Continuous variables will be analyzed in three ways. First, summary statistics and graphical&#xD;
      presentation of results will be performed for each of baseline and months 3 and 6. Second,&#xD;
      change from baseline to month 6 will be compared using a paired t-test, or a Mann-Whitney&#xD;
      test if distributional assumptions do not hold. A subject's last available, or exit visit,&#xD;
      will be used if their month 6 visit is not available. Third, longitudinal random-effects&#xD;
      models will be used to model the trajectory of each outcome over time and to determine the&#xD;
      influence of randomized intervention group on that trajectory. Variables may be transformed&#xD;
      to satisfy the assumptions of normally distributed random effects, but results will be&#xD;
      presented on the original scale.&#xD;
&#xD;
      Sample Size Justification:&#xD;
&#xD;
      The primary null hypothesis compares the probability of a patient being in control in either&#xD;
      experimental group to the Standard of Care group:&#xD;
&#xD;
      H0: pSoC ≥ pIWL and pSoC ≥ pSTP vs. H1: pSoC &lt; pIWL or pSoC &lt; pSTP&#xD;
&#xD;
      Based on data observed within the clinic from which cases are to be recruited, the success&#xD;
      rate for Standard of Care patients is estimated to about 75%. A sample size of 200 subjects&#xD;
      in a 2:1:1 randomization to the SoC, STP and IWL and groups respectively will provide a power&#xD;
      of over 95% to reject the null hypothesis if the true difference between SoC and either&#xD;
      experimental arm is 25% or greater (eg: 37.5% compared to 62.5%).&#xD;
&#xD;
      In addition, this sample size provides a power of more than 74% to reject the null hypothesis&#xD;
      in favor of the alternative hypothesis that the percent of patients achieving control is&#xD;
      greater among both the STP and IWL than among the SoC, if the true difference between arms is&#xD;
      25% or greater.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 2018</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Three months average blood glucose (A1c)</measure>
    <time_frame>at 3 months and 6 months</time_frame>
    <description>We will assess the effect of supervised training and financially incentivized weight loss on three month average blood glucose in patients with diabetes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>apo B</measure>
    <time_frame>6 months</time_frame>
    <description>proportion of patientst achieving apoB &lt;0.8 mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>systolic blood pressure (SBP)</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>proportion of patients achieving SBP &lt; 140 mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A1c</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>proportion of patients achieving A1c &lt; 7.0%</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Composite: Psychosocial outcomes are depressive symptoms, Diabetes specific quality of life</measure>
    <time_frame>3 months and 6 months,</time_frame>
    <description>this composite outcome will reflect overall change in QoL scoring during study</description>
  </other_outcome>
  <other_outcome>
    <measure>waist circumference</measure>
    <time_frame>3 months and 6 months,</time_frame>
    <description>Waist circumference</description>
  </other_outcome>
  <other_outcome>
    <measure>weight</measure>
    <time_frame>3 months and 6 months,</time_frame>
    <description>weight</description>
  </other_outcome>
  <other_outcome>
    <measure>body mass index (BMI)</measure>
    <time_frame>3 months and 6 months,</time_frame>
    <description>BMI</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>Financially incentivized weight loss</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants can be assigned to the financially incentivized weight loss group in which they can receive 50 dollars at the end of the month if they achieve their monthly weight loss goal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants can be assigned to standard of care where they receive no intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Supervised Exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants can be assigned to the supervised exercise arm which they will receive supervised professional training once a week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Supervised exercise</intervention_name>
    <description>Supervised exercise intervention is training with professional trainers once a week. It will include aerobic exercise tailored to the individual participant.</description>
    <arm_group_label>Supervised Exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Financially incentivized weight Loss</intervention_name>
    <description>Financially incentivized weight loss encourages participants to achieve a monthly goal weight reduction for a 50 dollars prize.</description>
    <arm_group_label>Financially incentivized weight loss</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Care at BCDiabetes</intervention_name>
    <description>usual care dictated by GCP at BCDiabetes.ca</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 or older.&#xD;
&#xD;
          2. Have been diagnosed with Type 2 diabetes by CDA guidelines.&#xD;
&#xD;
          3. A1c &gt; 8.0 no more than 30 days prior to randomization and confirmed at the time of&#xD;
             randomization.&#xD;
&#xD;
          4. Overweight or obese as defined by BMI of &gt;25.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have medical co-morbidities that limit their exercise capacity (terminal cancer,&#xD;
             severe physical disability such as limb amputation, blindness, seizure disorder,&#xD;
             strokes with residual deficits, arrhythmias that would limit physical activity).&#xD;
&#xD;
          2. Alcohol or drug abuse that would interfere with exercise regimen.&#xD;
&#xD;
          3. Cannot read or write English (with the assistance of an interpreter) or are unable to&#xD;
             fill out logs and questionnaire.&#xD;
&#xD;
          4. Inability or unwillingness of subject or legal guardian/representative to give written&#xD;
             informed consent.&#xD;
&#xD;
          5. Patients for whom an exercise program is deemed medically inadvisable.&#xD;
&#xD;
          6. Patients already enrolled in a supervised training program.&#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>Tom Elliott, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BCDiabetes.Ca</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mandana Moosavi, MDCM</last_name>
    <phone>6043604704</phone>
    <email>mandana.moosavi@mail.mcgill.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tom Elliott, MD</last_name>
    <phone>6046752491</phone>
    <email>telliott@bcdiabetes.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Vancouver General Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <investigator>
      <last_name>Tom Elliott, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.</citation>
    <PMID>19896746</PMID>
  </reference>
  <reference>
    <citation>Klein S, Sheard NF, Pi-Sunyer X, Daly A, Wylie-Rosett J, Kulkarni K, Clark NG; American Diabetes Association; North American Association for the Study of Obesity; American Society for Clinical Nutrition. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Am J Clin Nutr. 2004 Aug;80(2):257-63. doi: 10.1093/ajcn/80.2.257.</citation>
    <PMID>15277143</PMID>
  </reference>
  <reference>
    <citation>Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr. 2003 Oct;22(5):331-9. doi: 10.1080/07315724.2003.10719316.</citation>
    <PMID>14559925</PMID>
  </reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>February 16, 2017</last_update_submitted>
  <last_update_submitted_qc>February 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>BCDiabetes.Ca</investigator_affiliation>
    <investigator_full_name>Tom Elliott</investigator_full_name>
    <investigator_title>Clinical Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Diabetes</keyword>
  <keyword>Supervised Exercise</keyword>
  <keyword>Weight loss</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to share IPD to other researchers except those involved in the trial</ipd_description>
  </patient_data>
  <!-- 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/NCT02210845
org study id: DOS-23
nct id: NCT02210845
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to investigate whether a behavioral modification intervention
      in the form of either a 6-month supervised training program or a 6-month financial incentive
      weight loss program, results in improvement of diabetes outcome such as overall sugar control
      and lipid control.
This is a single-center, prospective, unblinded, randomized, controlled, clinical trial of
      200 subjects randomized to either a Supervised Training Program (STP), Incentivized Weight
      Loss (IWL) or Standard of Care (SoC).

      Subjects randomized to the SoC group will be asked to return for regular 3-monthly clinic
      visits and for diet and exercise recommendations.The STP group will be offered once-weekly
      one hour supervised training sessions at no charge for a period of six months in the
      bcdiabetes.ca fitness center (located in the Vancouver General Hospital Employee Centre gym).

      The IWL group will receive a financial reward for achieving monthly weight loss targets.
      Those who fail to meet their monthly goals will receive no financial reward. Such financial
      incentives have been considered in previous research. Due to the nature of the intervention,
      none of the investigative staff, trainers or subjects will be blinded to randomized
      assignment.

      The primary objective of this study is to investigate whether a behavioral modification
      intervention in the form of either a 6-month supervised training program or a 6-month
      financial incentive program, results in overall superior clinical outcomes in comparison to
      standard of care. Specifically, improvement in glucose control, measured by A1c, will be
      considered. Given the objective nature of the Primary Outcome, there is little possibility of
      assessment bias of the primary or clinical outcomes.The secondary objective is to investigate
      the impact of a supervised training program and an incentivized weight loss program on
      weight-loss, LDL (apoB), blood pressure, waist-hip circumference, and diabetes-specific
      quality of life measures including behavioral and emotional impact (refer to Secondary
      Outcomes section).

      Patients attending BCDiabetes ( Diabetes Clinic at Diamond Center )will be approached by one
      of their diabetes caregivers who will describe the study and determine whether they have
      interest in participating. If the patient expresses an interest, they will be provided
      additional information and a study consent form and be free to ask questions about the study.
      They may choose to provide consent at the time or to leave with the consent form and return
      at a later time to ask further questions. A research nurse, coordinator and/or co/principal
      investigator will be available to answer any questions the patient may have. When consent is
      provided, confirmation of the eligibility criteria will be completed and the subject will
      receive their randomized group assignment.

      Eligible subjects will be randomized in a 2:1:1 fashion to the SoC, STP and IWL and groups
      respectively. Randomization will be stratified by age (≤ 50 vs > 50 years of age) to ensure
      balance in age groups in all three treatment arms; enrollment will not be stratified and the
      number of participants in the two age groups will not be restricted. Randomization within
      strata will be done in a permuted complete block design with random block sizes (blocks no
      smaller than 6 and no larger than 15). Randomization will be completed in advance and
      assignments will be kept in individual, separate sealed, sequentially labeled envelopes
      opened at the time of randomization of each individual.

      Withdrawal from Study or Intervention:

      Although they should be encouraged to continue participation in their randomized group,
      subjects can choose to withdraw from the study, or to withdraw from the intervention at any
      time. Subjects who choose to withdraw from the STP and IWL arms should continue to receive
      standard of care and will be considered cross-overs to SoC arm; these subjects are not
      necessarily withdrawing from the study and should be encouraged to continue to return for
      their scheduled 3 and 6 month study visits so study outcomes can be measured. If a subject
      chooses to withdraw from the study entirely, all attempts should be made to have them
      complete an exit visit where all study outcomes can be captured.

      Subjects who experience any adverse event related to the STP arm (eg: physical injury while
      training) or experience the onset or worsening of an signs or symptoms related to a medical
      condition (eg: shortness of breath, dizziness, vomiting nausea, etc) persisting the day
      following a supervised training session, or who experience a worsening of a physical
      condition (eg: degenerative disc disorder, knee or hip pain, plantar fasciitis, etc) will be
      withdrawn from the STP intervention. As above, these subjects will be asked to return for
      their scheduled 3 and 6 month clinic visits.

      If at any point more than 15% of subjects in the STP arm are withdrawn from the intervention
      arm due to an adverse event, worsening medical or physical condition, the study will be
      stopped.

      Study data will be collected as part of the subject's electronic medical record at
      bcdiabetes.ca. Identifiable study data will be housed exclusively on bcdiabetes.ca; if
      removed from bcdiabetes.ca servers, subjects will be identified only with a study
      registration number different from their BC CareID number. Remote monitoring by EMMES using
      confidential authenticated automatically scheduled direct database queries. EMMES Canada will
      also provide oversight of quality assurance & monitoring.

      The primary outcome measure is the percent of subjects who achieve target for A1c. The null
      and research hypothesis supporting the primary objective of investigating the impact of
      whether a behavioral modification intervention in the form of either a 6-month supervised
      training program or a 6-month incentivized weight loss program, results in overall superior
      clinical outcomes in comparison to standard of care is then:

      H0: pSoC ≥ pIWL and pSoC ≥ pSTP vs. H1: pSoC < pIWL or pSoC < pSTP

      where pSoC , pSTP and pIWL are the proportion of subjects achieving the target for all three
      disease measures. Here, rejecting the null hypothesis implies that the percent of patients
      achieving targets is higher in either of the STP arm or the IWL arm than in the SoC arm. A
      one-sided, 0.05 alpha-level simultaneous test for multiple contrasts of binomial proportions
      with an "Add-2" adjustment will be used.

      The primary analysis cohort will be an ITT cohort including all randomized subjects and
      considering the arm to which they were originally randomized regardless of adherence to the
      regimen or the study protocol. Subjects who cross-over to the other intervention prior to
      Month 3 (ie: complete less than 3 of the required 6 months) will be considered failures in
      the arm to which they were originally randomized. Clinical data from the last, or exit visit
      will be used to construct the primary outcome for subjects who withdraw from the study, or
      from the intervention, subsequent to Month 3.

      To corroborate the primary, unadjusted analysis, a logistic regression model will be fit with
      baseline clinical and demographic data as well as measures of compliance to intervention to
      adjust for possible imbalance of important variables. Also, the primary analysis will be
      repeated on a per-protocol cohort of subjects who completed the study according to the
      protocol and did not cross-over or withdraw from therapy. Graphical techniques and summary
      statistics for the two randomized groups at baseline and months 3 and 6 will also be
      presented.

      Summary statistics and graphical presentations will be used to summarize data for all
      secondary outcomes. All hypothesis tests will be 2-sided and with a 5% Type I error
      probability. There will be no adjustment for multiple comparisons among the secondary
      outcomes with the exception that multiple domains within a single psychosocial instrument
      (eg: emotional burden, physician-related distress, regimen-related distress, and
      diabetes-related interpersonal distress domains within the DDS) will be subject to a
      Benjamini-Hochberg multiple comparison adjustment. Analyses will be conducted on the ITT
      cohort and corroborated by analysis on the per-protocol cohort.

      Each clinical outcome measure is captured as a continuous and dichotomized variable (eg: A1c
      absolute level and those < 7.0%). Dichotomized variables will be analyzed as described in the
      Primary Analysis.

      Continuous variables will be analyzed in three ways. First, summary statistics and graphical
      presentation of results will be performed for each of baseline and months 3 and 6. Second,
      change from baseline to month 6 will be compared using a paired t-test, or a Mann-Whitney
      test if distributional assumptions do not hold. A subject's last available, or exit visit,
      will be used if their month 6 visit is not available. Third, longitudinal random-effects
      models will be used to model the trajectory of each outcome over time and to determine the
      influence of randomized intervention group on that trajectory. Variables may be transformed
      to satisfy the assumptions of normally distributed random effects, but results will be
      presented on the original scale.

      Sample Size Justification:

      The primary null hypothesis compares the probability of a patient being in control in either
      experimental group to the Standard of Care group:

      H0: pSoC ≥ pIWL and pSoC ≥ pSTP vs. H1: pSoC < pIWL or pSoC < pSTP

      Based on data observed within the clinic from which cases are to be recruited, the success
      rate for Standard of Care patients is estimated to about 75%. A sample size of 200 subjects
      in a 2:1:1 randomization to the SoC, STP and IWL and groups respectively will provide a power
      of over 95% to reject the null hypothesis if the true difference between SoC and either
      experimental arm is 25% or greater (eg: 37.5% compared to 62.5%).

      In addition, this sample size provides a power of more than 74% to reject the null hypothesis
      in favor of the alternative hypothesis that the percent of patients achieving control is
      greater among both the STP and IWL than among the SoC, if the true difference between arms is
      25% or greater.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Three months average blood glucose (A1c)
time frame: at 3 months and 6 months
description: We will assess the effect of supervised training and financially incentivized weight loss on three month average blood glucose in patients with diabetes.
measure: apo B
time frame: 6 months
description: proportion of patientst achieving apoB <0.8 mmol/L
measure: systolic blood pressure (SBP)
time frame: 3 months and 6 months
description: proportion of patients achieving SBP < 140 mmHg
measure: A1c
time frame: 3 months and 6 months
description: proportion of patients achieving A1c < 7.0%
measure: Composite: Psychosocial outcomes are depressive symptoms, Diabetes specific quality of life
time frame: 3 months and 6 months,
description: this composite outcome will reflect overall change in QoL scoring during study
measure: waist circumference
time frame: 3 months and 6 months,
description: Waist circumference
measure: weight
time frame: 3 months and 6 months,
description: weight
measure: body mass index (BMI)
time frame: 3 months and 6 months,
description: BMI
arm group label: Financially incentivized weight loss
arm group type: Active Comparator
description: Participants can be assigned to the financially incentivized weight loss group in which they can receive 50 dollars at the end of the month if they achieve their monthly weight loss goal.
arm group label: Standard of Care
arm group type: Placebo Comparator
description: Participants can be assigned to standard of care where they receive no intervention.
arm group label: Supervised Exercise
arm group type: Active Comparator
description: Participants can be assigned to the supervised exercise arm which they will receive supervised professional training once a week.
intervention type: Behavioral
intervention name: Supervised exercise
description: Supervised exercise intervention is training with professional trainers once a week. It will include aerobic exercise tailored to the individual participant.
arm group label: Supervised Exercise
intervention type: Behavioral
intervention name: Financially incentivized weight Loss
description: Financially incentivized weight loss encourages participants to achieve a monthly goal weight reduction for a 50 dollars prize.
arm group label: Financially incentivized weight loss
intervention type: Other
intervention name: Standard Care at BCDiabetes
description: usual care dictated by GCP at BCDiabetes.ca
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Tom Elliott, MD
role: Principal Investigator
affiliation: BCDiabetes.Ca
last name: Mandana Moosavi, MDCM
phone: 6043604704
email: mandana.moosavi@mail.mcgill.ca
last name: Tom Elliott, MD
phone: 6046752491
email: telliott@bcdiabetes.ca
facility: 
investigator: 
country: Canada
citation: Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.
PMID: 19896746
citation: Klein S, Sheard NF, Pi-Sunyer X, Daly A, Wylie-Rosett J, Kulkarni K, Clark NG; American Diabetes Association; North American Association for the Study of Obesity; American Society for Clinical Nutrition. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Am J Clin Nutr. 2004 Aug;80(2):257-63. doi: 10.1093/ajcn/80.2.257.
PMID: 15277143
citation: Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr. 2003 Oct;22(5):331-9. doi: 10.1080/07315724.2003.10719316.
PMID: 14559925
responsible party type: Sponsor-Investigator
investigator affiliation: BCDiabetes.Ca
investigator full name: Tom Elliott
investigator title: Clinical Associate Professor
mesh term: Diabetes Mellitus
sharing ipd: No
ipd description: There is no plan to share IPD to other researchers except those involved in the trial