<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/NCT03263351</url>
  </required_header>
  <id_info>
    <org_study_id>4185</org_study_id>
    <secondary_id>R01DK111604</secondary_id>
    <nct_id>NCT03263351</nct_id>
  </id_info>
  <brief_title>Depression &amp; Insulin Sensitivity in Adolescents</brief_title>
  <official_title>Depression and Insulin Sensitivity in Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Colorado State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Colorado</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Colorado State 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>
      There has been a rise in type 2 diabetes (T2D) rates in adolescents, disproportionately in&#xD;
      girls from disadvantaged racial/ethnic groups. This group of girls also is at heightened risk&#xD;
      for depression, and depression and T2D are linked. Depressive symptoms are a risk factor for&#xD;
      worsening of insulin sensitivity, one if the major precursors to T2D. In preliminary studies,&#xD;
      the investigators found that a brief cognitive-behavioral therapy group decreased depressive&#xD;
      symptoms and prevented worsening of insulin sensitivity in adolescent girls at-risk for T2D&#xD;
      with moderate depressive symptoms. The aims of this study are: 1) to assess the efficacy of a&#xD;
      cognitive-behavioral therapy depression group vs. a health education control group for&#xD;
      improving insulin sensitivity and preserving insulin secretion in racially/ethnically diverse&#xD;
      adolescent girls at-risk for T2D with moderate depressive symptoms over a 1-year follow-up;&#xD;
      2) to evaluate changes in eating, physical activity, and sleep as explanatory and 3) to test&#xD;
      changes in cortisol factors as explanatory.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There has been rapid escalation of type 2 diabetes (T2D) rates in adolescents. Early-onset&#xD;
      T2D (&lt;20y) typically shows a more aggressive course than adult-onset T2D and&#xD;
      disproportionately affects girls from disadvantaged, racial/ethnic groups. This group of&#xD;
      girls also is at heightened risk for depression, and depression and T2D are linked.&#xD;
      Depressive symptoms often manifest in adolescence and are a prospective risk factor for&#xD;
      worsening of insulin sensitivity, the major physiological precursor-in combination with&#xD;
      deterioration of pancreatic β-cell capacity to secrete insulin-in the path to T2D. The&#xD;
      effects of depression on poor insulin sensitivity remain even after accounting for adiposity.&#xD;
      In theory, depressive symptoms may worsen insulin sensitivity through stress-induced&#xD;
      behaviors (e.g., disinhibited eating, physical inactivity, sleep disturbance) and&#xD;
      stress-induced physiological causal mechanisms (e.g., hypercortisolism). The central theme of&#xD;
      this study is that intervening to reduce depressive symptoms in adolescents at-risk for T2D&#xD;
      may offer an innovative, targeted approach to ameliorate insulin resistance and to,&#xD;
      consequently, preserve β-cell function and lessen T2D risk. In preliminary data, the&#xD;
      investigators found initial evidence that a 6-week cognitive-behavioral group decreased&#xD;
      depressive symptoms and prevented worsening of insulin sensitivity 1 year later in overweight&#xD;
      and obese girls with moderate depressive symptoms and a family history of T2D, in comparison&#xD;
      to a 6-week health education control group. Directly extending these findings, the primary&#xD;
      aims of this study are: 1) to assess the efficacy of a 6-week cognitive-behavioral depression&#xD;
      group vs. a 6-week health education control group for improving insulin sensitivity and&#xD;
      preserving β-cell function in racially/ethnically diverse adolescent girls at-risk for T2D&#xD;
      with moderate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating,&#xD;
      physical activity, and sleep as behavioral explanatory mediators underlying the relationship&#xD;
      between decreases in depressive symptoms and improvements in insulin sensitivity and β-cell&#xD;
      function over 1 year and 3) to test changes in cortisol awakening response, diurnal cortisol&#xD;
      rhythm, and total daily cortisol output as physiological mechanisms explaining the&#xD;
      relationship between decreases in depressive symptoms and improvements in insulin sensitivity&#xD;
      and β-cell function over 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2023</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>
    <intervention_model_description>This is a randomized controlled behavioral trial with two conditions - cognitive-behavioral therapy group or health education group - run in parallel.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Research staff who assess outcomes will be blinded to condition assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Depressive symptoms</measure>
    <time_frame>1-year</time_frame>
    <description>Center for Epidemiologic Studies-Depression Scale (CES-D) total score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>1-year</time_frame>
    <description>Whole body insulin sensitivity index estimated from 2-hour oral glucose tolerance test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Insulin secretion</measure>
    <time_frame>1-year</time_frame>
    <description>Oral disposition index estimated from 2-hour oral glucose tolerance test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disinhibited eating</measure>
    <time_frame>1-year</time_frame>
    <description>Emotional Eating Scale adapted for Children depression scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical activity</measure>
    <time_frame>1-year</time_frame>
    <description>Moderate-to-vigorous physical activity by accelerometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical inactivity</measure>
    <time_frame>1-year</time_frame>
    <description>Sedentary time by accelerometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep</measure>
    <time_frame>1-year</time_frame>
    <description>Sleep duration by actigraphy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cortisol diurnal rhythm</measure>
    <time_frame>1-year</time_frame>
    <description>Salivary cortisol by home collection throughout the day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily cortisol output</measure>
    <time_frame>1-year</time_frame>
    <description>24-hour urine cortisol</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Type2 Diabetes</condition>
  <condition>Type 2 Diabetes Mellitus</condition>
  <condition>Insulin Sensitivity</condition>
  <condition>Insulin Resistance</condition>
  <condition>Depression</condition>
  <condition>Adolescent Obesity</condition>
  <arm_group>
    <arm_group_label>Cognitive-behavioral therapy group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Six-session cognitive-behavioral therapy group program designed as a prevention of depression intervention for adolescents at-risk for depression. The program is facilitated by a psychologist. Sessions are weekly for 1-hour.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Health education group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Six-session health education group program designed as a health education curriculum for teenagers. The program is facilitated by a psychologist. Sessions are weekly for 1-hour.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive-behavioral therapy group</intervention_name>
    <description>Psychoeducation on depression; cognitive restructuring of negative thoughts; engagement in pleasant activities; healthy rewards; stress and coping.</description>
    <arm_group_label>Cognitive-behavioral therapy group</arm_group_label>
    <other_name>Blues Program</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Health education group</intervention_name>
    <description>Didactic health knowledge about interpersonal violence; basic nutrition guidance; sun safety; depression and signs of suicide; gang violence; substance use.</description>
    <arm_group_label>Health education group</arm_group_label>
    <other_name>Hey-Durham</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Age 12-17 years&#xD;
&#xD;
          -  Body mass index (BMI) ≥85th percentile for age &amp; sex&#xD;
&#xD;
          -  Center for Epidemiologic Studies-Depression Scale (CES-D) &gt;20&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
          -  ≥1 first- or second-degree family member with type 2 diabetes (T2D), prediabetes, or&#xD;
             gestational diabetes&#xD;
&#xD;
          -  Good general health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Type 2 diabetes as indicated by fasting glucose≥126 mg/dL or 2-hour glucose&gt;200 mg/dL&#xD;
             or Hba1c&gt;=6.5&#xD;
&#xD;
          -  Medication affecting mood, weight, cortisol, or insulin sensitivity, including insulin&#xD;
             sensitizers (e.g., metformin), anti-depressants, and stimulants&#xD;
&#xD;
          -  Major psychiatric disorder that, in the opinion of the investigators, would impede&#xD;
             study compliance and necessitate more intensive treatment, including major depressive&#xD;
             disorder, bipolar disorder, posttraumatic stress disorder, panic disorder,&#xD;
             obsessive-compulsive disorder, schizophrenia, conduct disorder, alcohol and substance&#xD;
             abuse, and anorexia/bulimia nervosa&#xD;
&#xD;
          -  Psychotherapy or structured weight loss program&#xD;
&#xD;
          -  Active suicidal ideation or suicidal behavior&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Lauren B Shomaker, PhD</last_name>
    <phone>(970)491-3217</phone>
    <email>lauren.shomaker@colostate.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lauren Shomaker, PhD</last_name>
      <phone>720-777-3138</phone>
      <email>lauren.shomaker@childrenscolorado.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Andrews SA, Colvin HJ. Verification of Intoximeter 3000 breath alcohol concentration by magnesium perchlorate tube method in long-term field program. J Anal Toxicol. 1989 Mar-Apr;13(2):113-6. doi: 10.1093/jat/13.2.113.</citation>
    <PMID>2733389</PMID>
  </reference>
  <reference>
    <citation>Shomaker LB, Kelly NR, Radin RM, Cassidy OL, Shank LM, Brady SM, Demidowich AP, Olsen CH, Chen KY, Stice E, Tanofsky-Kraff M, Yanovski JA. Prevention of insulin resistance in adolescents at risk for type 2 diabetes with depressive symptoms: 1-year follow-up of a randomized trial. Depress Anxiety. 2017 Oct;34(10):866-876. doi: 10.1002/da.22617. Epub 2017 Mar 31.</citation>
    <PMID>28370947</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>July 28, 2023</last_update_submitted>
  <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Pediatric Obesity</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03263351
org study id: 4185
secondary id: R01DK111604
nct id: NCT03263351
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
There has been a rise in type 2 diabetes (T2D) rates in adolescents, disproportionately in
      girls from disadvantaged racial/ethnic groups. This group of girls also is at heightened risk
      for depression, and depression and T2D are linked. Depressive symptoms are a risk factor for
      worsening of insulin sensitivity, one if the major precursors to T2D. In preliminary studies,
      the investigators found that a brief cognitive-behavioral therapy group decreased depressive
      symptoms and prevented worsening of insulin sensitivity in adolescent girls at-risk for T2D
      with moderate depressive symptoms. The aims of this study are: 1) to assess the efficacy of a
      cognitive-behavioral therapy depression group vs. a health education control group for
      improving insulin sensitivity and preserving insulin secretion in racially/ethnically diverse
      adolescent girls at-risk for T2D with moderate depressive symptoms over a 1-year follow-up;
      2) to evaluate changes in eating, physical activity, and sleep as explanatory and 3) to test
      changes in cortisol factors as explanatory.
There has been rapid escalation of type 2 diabetes (T2D) rates in adolescents. Early-onset
      T2D (<20y) typically shows a more aggressive course than adult-onset T2D and
      disproportionately affects girls from disadvantaged, racial/ethnic groups. This group of
      girls also is at heightened risk for depression, and depression and T2D are linked.
      Depressive symptoms often manifest in adolescence and are a prospective risk factor for
      worsening of insulin sensitivity, the major physiological precursor-in combination with
      deterioration of pancreatic β-cell capacity to secrete insulin-in the path to T2D. The
      effects of depression on poor insulin sensitivity remain even after accounting for adiposity.
      In theory, depressive symptoms may worsen insulin sensitivity through stress-induced
      behaviors (e.g., disinhibited eating, physical inactivity, sleep disturbance) and
      stress-induced physiological causal mechanisms (e.g., hypercortisolism). The central theme of
      this study is that intervening to reduce depressive symptoms in adolescents at-risk for T2D
      may offer an innovative, targeted approach to ameliorate insulin resistance and to,
      consequently, preserve β-cell function and lessen T2D risk. In preliminary data, the
      investigators found initial evidence that a 6-week cognitive-behavioral group decreased
      depressive symptoms and prevented worsening of insulin sensitivity 1 year later in overweight
      and obese girls with moderate depressive symptoms and a family history of T2D, in comparison
      to a 6-week health education control group. Directly extending these findings, the primary
      aims of this study are: 1) to assess the efficacy of a 6-week cognitive-behavioral depression
      group vs. a 6-week health education control group for improving insulin sensitivity and
      preserving β-cell function in racially/ethnically diverse adolescent girls at-risk for T2D
      with moderate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating,
      physical activity, and sleep as behavioral explanatory mediators underlying the relationship
      between decreases in depressive symptoms and improvements in insulin sensitivity and β-cell
      function over 1 year and 3) to test changes in cortisol awakening response, diurnal cortisol
      rhythm, and total daily cortisol output as physiological mechanisms explaining the
      relationship between decreases in depressive symptoms and improvements in insulin sensitivity
      and β-cell function over 1 year.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized controlled behavioral trial with two conditions - cognitive-behavioral therapy group or health education group - run in parallel.
primary purpose: Prevention
masking: Single (Outcomes Assessor)
masking description: Research staff who assess outcomes will be blinded to condition assignment.
measure: Depressive symptoms
time frame: 1-year
description: Center for Epidemiologic Studies-Depression Scale (CES-D) total score
measure: Insulin sensitivity
time frame: 1-year
description: Whole body insulin sensitivity index estimated from 2-hour oral glucose tolerance test
measure: Insulin secretion
time frame: 1-year
description: Oral disposition index estimated from 2-hour oral glucose tolerance test
measure: Disinhibited eating
time frame: 1-year
description: Emotional Eating Scale adapted for Children depression scale
measure: Physical activity
time frame: 1-year
description: Moderate-to-vigorous physical activity by accelerometer
measure: Physical inactivity
time frame: 1-year
description: Sedentary time by accelerometer
measure: Sleep
time frame: 1-year
description: Sleep duration by actigraphy
measure: Cortisol diurnal rhythm
time frame: 1-year
description: Salivary cortisol by home collection throughout the day
measure: Daily cortisol output
time frame: 1-year
description: 24-hour urine cortisol
arm group label: Cognitive-behavioral therapy group
arm group type: Experimental
description: Six-session cognitive-behavioral therapy group program designed as a prevention of depression intervention for adolescents at-risk for depression. The program is facilitated by a psychologist. Sessions are weekly for 1-hour.
arm group label: Health education group
arm group type: Active Comparator
description: Six-session health education group program designed as a health education curriculum for teenagers. The program is facilitated by a psychologist. Sessions are weekly for 1-hour.
intervention type: Behavioral
intervention name: Cognitive-behavioral therapy group
description: Psychoeducation on depression; cognitive restructuring of negative thoughts; engagement in pleasant activities; healthy rewards; stress and coping.
arm group label: Cognitive-behavioral therapy group
other name: Blues Program
intervention type: Behavioral
intervention name: Health education group
description: Didactic health knowledge about interpersonal violence; basic nutrition guidance; sun safety; depression and signs of suicide; gang violence; substance use.
arm group label: Health education group
other name: Hey-Durham
criteria: 
gender: Female
minimum age: 12 Years
maximum age: 17 Years
healthy volunteers: No
last name: Lauren B Shomaker, PhD
phone: (970)491-3217
email: lauren.shomaker@colostate.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Andrews SA, Colvin HJ. Verification of Intoximeter 3000 breath alcohol concentration by magnesium perchlorate tube method in long-term field program. J Anal Toxicol. 1989 Mar-Apr;13(2):113-6. doi: 10.1093/jat/13.2.113.
PMID: 2733389
citation: Shomaker LB, Kelly NR, Radin RM, Cassidy OL, Shank LM, Brady SM, Demidowich AP, Olsen CH, Chen KY, Stice E, Tanofsky-Kraff M, Yanovski JA. Prevention of insulin resistance in adolescents at risk for type 2 diabetes with depressive symptoms: 1-year follow-up of a randomized trial. Depress Anxiety. 2017 Oct;34(10):866-876. doi: 10.1002/da.22617. Epub 2017 Mar 31.
PMID: 28370947
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
mesh term: Pediatric Obesity
mesh term: Hypersensitivity
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: No