<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/NCT02970656</url>
  </required_header>
  <id_info>
    <org_study_id>1503015414</org_study_id>
    <nct_id>NCT02970656</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Biomarkers of Stress in Youth Who Use Teens.Connect</brief_title>
  <official_title>A Pilot Study of Biomarkers of Stress in Youth Who Use Teens.Connect</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Miller Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale 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>
      This feasibility/pilot study has three purposes. First, the investigators will determine the&#xD;
      feasibility of collecting saliva to measure stress biomarkers over three days at home in&#xD;
      youth. Second, the investigators will conduct a pilot study of the Teens.Connect Internet&#xD;
      program for youth with type 1 diabetes to determine whether changes in stress biomarkers&#xD;
      associate with self-reported perceived stress and HbA1c. Third, the investigators will&#xD;
      examine the gene-environment interaction of the top 14 targeted candidate genes and&#xD;
      epi-genome wide effects of teens' stress biomarkers and its influence on blood glucose levels&#xD;
      over time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intensive management of type 1 diabetes (T1D) among youth as recommended by the American&#xD;
      Diabetes Association requires a complex set of self-management activities that create high&#xD;
      levels of perceived stress in youth and families. In individuals exposed to chronic stress,&#xD;
      such as that of a chronic condition, the body responds with physiological and hormonal&#xD;
      responses to adapt. These responses can be harmful (e.g., higher glucose levels, higher&#xD;
      HbA1c). Such harmful effects may be ameliorated by programs that reduce psychosocial stress.&#xD;
&#xD;
      The investigators have found an Internet-delivered coping skills training program combined&#xD;
      with a diabetes education program significantly improved HbA1c and QOL for youth with T1D.&#xD;
      Self-reported perceived stress mediated these outcomes. There has been little to no&#xD;
      examination, however, of whether a reduction in self-reported perceived stress is associated&#xD;
      with a reduction in biochemical markers of stress which could explain the positive impact on&#xD;
      HbA1c. It is critically important to understand the physiologic as well as the psychosocial&#xD;
      mechanisms associated with such interventions in order to improve glycemic control in youth&#xD;
      with this chronic autoimmune condition. If such interventions affect biomarkers of stress, it&#xD;
      would be important to strengthen the stress reduction activities embedded in such&#xD;
      interventions, such as meditation, to further improve metabolic control. Thus, aims of this&#xD;
      pilot/feasibility study are to:&#xD;
&#xD;
        1. Determine the feasibility and reliability of collection of saliva for the measurement of&#xD;
           three stress biomarkers at awakening and 30-45 minutes later over 3 days at home in 20&#xD;
           youth (age 11-14 years). These biomarkers include cortisol to assess&#xD;
           hypothalamic-pituitary-adrenal axis functioning; alpha-amylase (s-AA) to assess the&#xD;
           sympathetic-adrenal-medullary system, and salivary immunoglobulin A (s-IgA) to assess&#xD;
           stress-related immune changes. This aim will allow the investigators to determine the&#xD;
           feasibility of recruiting youth to provide such data in a larger trial by assessing the&#xD;
           percent of youth who agree to participate and adhere to the salivary collection&#xD;
           protocol, using actigraphy to document awakening time and Medication Event Monitoring&#xD;
           System (MEMS) caps monitoring to determine time of salivary collection. Patterns and&#xD;
           variability of stress biomarker levels over 3 days will be used to assess&#xD;
           intra-individual variability and relationships with self-reported daily stressors and&#xD;
           self-reported perceived stress.&#xD;
&#xD;
        2. Conduct a pilot study of Teens.Connect, a combination of the investigators' previous&#xD;
           TEENCOPE™ and Managing Diabetes programs with 40 youth to determine whether alterations&#xD;
           in stress biomarkers are associated with self-reported perceived stress and HbA1c.&#xD;
&#xD;
        3. Assess epigenetic components of these responses by examining the gene-environment&#xD;
           interaction of the top 14 targeted candidate genes and epigenome wide effects of teens'&#xD;
           stress biomarkers and their influence on HbA1c levels over time. Candidate genes will be&#xD;
           measured at baseline and DNA methylation patterns will be measured at baseline and then&#xD;
           again at 6 months follow-up using the Oragene saliva collection kits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2017</start_date>
  <completion_date type="Actual">February 28, 2019</completion_date>
  <primary_completion_date type="Actual">February 28, 2019</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>Glycosylated Hemoglobin (HbA1c)</measure>
    <time_frame>baseline</time_frame>
    <description>Bayer Diagnostics DCA2000® (normal range = 4.2-6.3%)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glycosylated Hemoglobin (HbA1c)</measure>
    <time_frame>6 months</time_frame>
    <description>Bayer Diagnostics DCA2000® (normal range = 4.2-6.3%)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Perceived Stress Scale</measure>
    <time_frame>baseline</time_frame>
    <description>A 14-item scale that measures the degree to which situations in one's life are appraised as stressful. Items assess feelings of stress, hassles, and coping during the past month. Respondents rate items on a 5-point Likert scale ranging from 0 (never) to 4 (very often), with higher scores indicative of greater perceived stress and less effective coping.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived Stress Scale</measure>
    <time_frame>6 months</time_frame>
    <description>A 14-item scale that measures the degree to which situations in one's life are appraised as stressful. Items assess feelings of stress, hassles, and coping during the past month. Respondents rate items on a 5-point Likert scale ranging from 0 (never) to 4 (very often), with higher scores indicative of greater perceived stress and less effective coping.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adolescent Stress Questionnaire (ASQ)</measure>
    <time_frame>baseline</time_frame>
    <description>A 94-item inventory of common adolescent stressors. Each item (stressor) is rated on a 5-point Likert scale where 1=Not at all stressful (or is irrelevant to me); 2=A little stressful; 3=Moderately stressful; 4=Quite stressful; and 5=Very stressful.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adolescent Stress Questionnaire (ASQ)</measure>
    <time_frame>6 months</time_frame>
    <description>A 94-item inventory of common adolescent stressors. Each item (stressor) is rated on a 5-point Likert scale where 1=Not at all stressful (or is irrelevant to me); 2=A little stressful; 3=Moderately stressful; 4=Quite stressful; and 5=Very stressful.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responses to Stress Questionnaire for Diabetes (RSQ)</measure>
    <time_frame>baseline</time_frame>
    <description>A 69-item scale asking the participant to report frequency of diabetes related stressors (12 items) and their responses to those stressors (57 items). Frequencies are reported on a 4-point scale ranging from 0 (never) to 3 (almost every day) for stressors, and 1 (not at all) to 4 (a lot) for stress responses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responses to Stress Questionnaire for Diabetes (RSQ)</measure>
    <time_frame>6 months</time_frame>
    <description>A 69-item scale asking the participant to report frequency of diabetes related stressors (12 items) and their responses to those stressors (57 items). Frequencies are reported on a 4-point scale ranging from 0 (never) to 3 (almost every day) for stressors, and 1 (not at all) to 4 (a lot) for stress responses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stress Biomarkers</measure>
    <time_frame>over 3 days at baseline</time_frame>
    <description>cortisol, alpha-amylase (s-AA), and salivary immunoglobulin A (s-IgA) determined by salivary collection at awakening and 30-45 minutes later over 3 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stress Biomarkers</measure>
    <time_frame>over 2 days at 6 months</time_frame>
    <description>cortisol, alpha-amylase (s-AA), and salivary immunoglobulin A (s-IgA) determined by salivary collection at awakening and 30-45 minutes later over 2 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Awakening and sleep time</measure>
    <time_frame>over 3 days at baseline</time_frame>
    <description>wrist-worn accelerometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Awakening and sleep time</measure>
    <time_frame>over 2 days at 6 months</time_frame>
    <description>wrist-worn accelerometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotype &amp; DNA Methylation</measure>
    <time_frame>baseline</time_frame>
    <description>Saliva collection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DNA Methylation</measure>
    <time_frame>6 months</time_frame>
    <description>Saliva collection</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Teens.Connect</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Teens-Connect internet-based program has two complementary components - TEENCOPE and Managing Diabetes. Managing Diabetes consists of 5 sessions on educational content related to diabetes self management targeted to adolescents. TEENCOPE consists of a series of 5 sessions designed to increase children's sense of competence and mastery by retraining inappropriate or non-constructive coping styles and forming more positive styles and patterns of behavior. Each week a new 30-45 minute session is uploaded to a password-protected website on the Yale server for youth to complete. Youth are grouped with 8-12 peers who complete the same weekly sessions in an asynchronous manner. Youth interact with each other on an online discussion board moderated by a clinical psychologist.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Wait listing will serve as the control condition. Usual care at the Yale Pediatric Diabetes Center consists of quarterly visits with physicians and nurse practitioners, accessibility to nutritional and psychological consultation, and 24/7 on call service. Following completion of the 6 month data point, youth will be offered the opportunity to participate in the internet program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Teens.Connect</intervention_name>
    <description>Teens.Connect combines two internet psycho-educational programs, TEENCOPE™, an internet version of coping skills training using a graphic novel format combined with social media, and an internet diabetes problem-solving educational program (Managing Diabetes)</description>
    <arm_group_label>Teens.Connect</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosed with T1D for at least 6 months;&#xD;
&#xD;
          -  age 11 to 14 years&#xD;
&#xD;
          -  naïve to TEENCOPE and/or Managing Diabetes&#xD;
&#xD;
          -  assent and parent/guardian consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  medical condition that impacts cortisol functioning&#xD;
&#xD;
          -  takes medications that impact cortisol, except diabetes medications&#xD;
&#xD;
          -  sleeps less than 6 hours per night&#xD;
&#xD;
          -  smokes&#xD;
&#xD;
          -  takes oral contraceptives&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>11 Years</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Margaret Grey, DrPH, RN</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale School of Nursing</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jacquelyn Taylor, PhD, PNP-BC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale School of Nursing</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale School of Nursing</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516-7399</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>April 1, 2019</last_update_submitted>
  <last_update_submitted_qc>April 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2019</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, Type 1</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/NCT02970656
org study id: 1503015414
nct id: NCT02970656
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This feasibility/pilot study has three purposes. First, the investigators will determine the
      feasibility of collecting saliva to measure stress biomarkers over three days at home in
      youth. Second, the investigators will conduct a pilot study of the Teens.Connect Internet
      program for youth with type 1 diabetes to determine whether changes in stress biomarkers
      associate with self-reported perceived stress and HbA1c. Third, the investigators will
      examine the gene-environment interaction of the top 14 targeted candidate genes and
      epi-genome wide effects of teens' stress biomarkers and its influence on blood glucose levels
      over time.
Intensive management of type 1 diabetes (T1D) among youth as recommended by the American
      Diabetes Association requires a complex set of self-management activities that create high
      levels of perceived stress in youth and families. In individuals exposed to chronic stress,
      such as that of a chronic condition, the body responds with physiological and hormonal
      responses to adapt. These responses can be harmful (e.g., higher glucose levels, higher
      HbA1c). Such harmful effects may be ameliorated by programs that reduce psychosocial stress.

      The investigators have found an Internet-delivered coping skills training program combined
      with a diabetes education program significantly improved HbA1c and QOL for youth with T1D.
      Self-reported perceived stress mediated these outcomes. There has been little to no
      examination, however, of whether a reduction in self-reported perceived stress is associated
      with a reduction in biochemical markers of stress which could explain the positive impact on
      HbA1c. It is critically important to understand the physiologic as well as the psychosocial
      mechanisms associated with such interventions in order to improve glycemic control in youth
      with this chronic autoimmune condition. If such interventions affect biomarkers of stress, it
      would be important to strengthen the stress reduction activities embedded in such
      interventions, such as meditation, to further improve metabolic control. Thus, aims of this
      pilot/feasibility study are to:

        1. Determine the feasibility and reliability of collection of saliva for the measurement of
           three stress biomarkers at awakening and 30-45 minutes later over 3 days at home in 20
           youth (age 11-14 years). These biomarkers include cortisol to assess
           hypothalamic-pituitary-adrenal axis functioning; alpha-amylase (s-AA) to assess the
           sympathetic-adrenal-medullary system, and salivary immunoglobulin A (s-IgA) to assess
           stress-related immune changes. This aim will allow the investigators to determine the
           feasibility of recruiting youth to provide such data in a larger trial by assessing the
           percent of youth who agree to participate and adhere to the salivary collection
           protocol, using actigraphy to document awakening time and Medication Event Monitoring
           System (MEMS) caps monitoring to determine time of salivary collection. Patterns and
           variability of stress biomarker levels over 3 days will be used to assess
           intra-individual variability and relationships with self-reported daily stressors and
           self-reported perceived stress.

        2. Conduct a pilot study of Teens.Connect, a combination of the investigators' previous
           TEENCOPE™ and Managing Diabetes programs with 40 youth to determine whether alterations
           in stress biomarkers are associated with self-reported perceived stress and HbA1c.

        3. Assess epigenetic components of these responses by examining the gene-environment
           interaction of the top 14 targeted candidate genes and epigenome wide effects of teens'
           stress biomarkers and their influence on HbA1c levels over time. Candidate genes will be
           measured at baseline and DNA methylation patterns will be measured at baseline and then
           again at 6 months follow-up using the Oragene saliva collection kits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Glycosylated Hemoglobin (HbA1c)
time frame: baseline
description: Bayer Diagnostics DCA2000® (normal range = 4.2-6.3%)
measure: Glycosylated Hemoglobin (HbA1c)
time frame: 6 months
description: Bayer Diagnostics DCA2000® (normal range = 4.2-6.3%)
measure: Perceived Stress Scale
time frame: baseline
description: A 14-item scale that measures the degree to which situations in one's life are appraised as stressful. Items assess feelings of stress, hassles, and coping during the past month. Respondents rate items on a 5-point Likert scale ranging from 0 (never) to 4 (very often), with higher scores indicative of greater perceived stress and less effective coping.
measure: Perceived Stress Scale
time frame: 6 months
description: A 14-item scale that measures the degree to which situations in one's life are appraised as stressful. Items assess feelings of stress, hassles, and coping during the past month. Respondents rate items on a 5-point Likert scale ranging from 0 (never) to 4 (very often), with higher scores indicative of greater perceived stress and less effective coping.
measure: Adolescent Stress Questionnaire (ASQ)
time frame: baseline
description: A 94-item inventory of common adolescent stressors. Each item (stressor) is rated on a 5-point Likert scale where 1=Not at all stressful (or is irrelevant to me); 2=A little stressful; 3=Moderately stressful; 4=Quite stressful; and 5=Very stressful.
measure: Adolescent Stress Questionnaire (ASQ)
time frame: 6 months
description: A 94-item inventory of common adolescent stressors. Each item (stressor) is rated on a 5-point Likert scale where 1=Not at all stressful (or is irrelevant to me); 2=A little stressful; 3=Moderately stressful; 4=Quite stressful; and 5=Very stressful.
measure: Responses to Stress Questionnaire for Diabetes (RSQ)
time frame: baseline
description: A 69-item scale asking the participant to report frequency of diabetes related stressors (12 items) and their responses to those stressors (57 items). Frequencies are reported on a 4-point scale ranging from 0 (never) to 3 (almost every day) for stressors, and 1 (not at all) to 4 (a lot) for stress responses.
measure: Responses to Stress Questionnaire for Diabetes (RSQ)
time frame: 6 months
description: A 69-item scale asking the participant to report frequency of diabetes related stressors (12 items) and their responses to those stressors (57 items). Frequencies are reported on a 4-point scale ranging from 0 (never) to 3 (almost every day) for stressors, and 1 (not at all) to 4 (a lot) for stress responses.
measure: Stress Biomarkers
time frame: over 3 days at baseline
description: cortisol, alpha-amylase (s-AA), and salivary immunoglobulin A (s-IgA) determined by salivary collection at awakening and 30-45 minutes later over 3 days
measure: Stress Biomarkers
time frame: over 2 days at 6 months
description: cortisol, alpha-amylase (s-AA), and salivary immunoglobulin A (s-IgA) determined by salivary collection at awakening and 30-45 minutes later over 2 days
measure: Awakening and sleep time
time frame: over 3 days at baseline
description: wrist-worn accelerometer
measure: Awakening and sleep time
time frame: over 2 days at 6 months
description: wrist-worn accelerometer
measure: Genotype & DNA Methylation
time frame: baseline
description: Saliva collection
measure: DNA Methylation
time frame: 6 months
description: Saliva collection
arm group label: Teens.Connect
arm group type: Experimental
description: The Teens-Connect internet-based program has two complementary components - TEENCOPE and Managing Diabetes. Managing Diabetes consists of 5 sessions on educational content related to diabetes self management targeted to adolescents. TEENCOPE consists of a series of 5 sessions designed to increase children's sense of competence and mastery by retraining inappropriate or non-constructive coping styles and forming more positive styles and patterns of behavior. Each week a new 30-45 minute session is uploaded to a password-protected website on the Yale server for youth to complete. Youth are grouped with 8-12 peers who complete the same weekly sessions in an asynchronous manner. Youth interact with each other on an online discussion board moderated by a clinical psychologist.
arm group label: Control
arm group type: No Intervention
description: Wait listing will serve as the control condition. Usual care at the Yale Pediatric Diabetes Center consists of quarterly visits with physicians and nurse practitioners, accessibility to nutritional and psychological consultation, and 24/7 on call service. Following completion of the 6 month data point, youth will be offered the opportunity to participate in the internet program.
intervention type: Behavioral
intervention name: Teens.Connect
description: Teens.Connect combines two internet psycho-educational programs, TEENCOPE™, an internet version of coping skills training using a graphic novel format combined with social media, and an internet diabetes problem-solving educational program (Managing Diabetes)
arm group label: Teens.Connect
criteria: 
gender: All
minimum age: 11 Years
maximum age: 14 Years
healthy volunteers: No
last name: Margaret Grey, DrPH, RN
role: Principal Investigator
affiliation: Yale School of Nursing
last name: Jacquelyn Taylor, PhD, PNP-BC
role: Principal Investigator
affiliation: Yale School of Nursing
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No