<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/NCT03307070</url>
  </required_header>
  <id_info>
    <org_study_id>2016P002823</org_study_id>
    <nct_id>NCT03307070</nct_id>
  </id_info>
  <brief_title>Adapted Cognitive Behavioral Treatment for Depression in Patients With Moderate to Severe Traumatic Brain Injury</brief_title>
  <official_title>Adapted Cognitive Behavioral Treatment for Depression in Patients With Moderate to Severe Traumatic Brain Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Spaulding Rehabilitation Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</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>
      Cognitive behavioral therapy for major depressive disorder (MDD) was adapted for individuals&#xD;
      with moderate to severe traumatic brain injury (TBI) (CBT-TBI). A structured, treatment&#xD;
      manual was developed.&#xD;
&#xD;
      The primary aim is to evaluate the acceptability and tolerability of, and adherence to,&#xD;
      CBT-TBI in a randomized waitlist-controlled, 12-week pilot trial (N=40).&#xD;
&#xD;
      The exploratory aim is to evaluate the potential efficacy of CBT-TBI for MDD in the&#xD;
      randomized pilot trial (N=40) and possible moderators and mediators of outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary aim of this study is to develop a highly acceptable, manualized treatment&#xD;
      (CBT-TBI) for MDD in patients with moderate to severe TBI. Initial feasibility data from a&#xD;
      small, open pilot will inform the randomized controlled trial. Primary analyses will examine&#xD;
      feasibility and acceptability of the intervention. The investigators will then pilot test the&#xD;
      efficacy of the intervention to reduce depressive symptoms (IDS-C) after 12 weeks compared to&#xD;
      a waitlist control group.&#xD;
&#xD;
      The proposed study involves the following points of contact: (1) Obtaining informed consent&#xD;
      and screening (may be broken up into multiple visits), (2) biweekly clinician assessments of&#xD;
      depressive and neuropsychiatric symptoms (weeks 2, 4, 6, 8, 10), (3) weekly self-report&#xD;
      assessments of depressive symptoms for those receiving the intervention, (4) 12 weekly&#xD;
      individual CBT-TBI sessions for those randomized to the intervention, (5) a comprehensive&#xD;
      assessment at week 12 (primary endpoint), which includes the neuropsychological battery, and&#xD;
      (6) a 3-month follow-up assessment for those who received the intervention. The week 12 visit&#xD;
      can be split into two parts, with the neuropsychological assessment occurring during the&#xD;
      second part, in order to accommodate subjects' potential limitations due to fatigue.&#xD;
      Procedures for this study were all conducted remotely after March 17, 2020.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2017</start_date>
  <completion_date type="Actual">November 28, 2022</completion_date>
  <primary_completion_date type="Actual">November 18, 2022</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>Crossover Assignment</intervention_model>
    <intervention_model_description>The study is a randomized, waitlist controlled trial. All participants randomized to waitlist were offered the opportunity to receive the intervention after completion of the waitlist.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility - retention/completion rates</measure>
    <time_frame>12 weeks</time_frame>
    <description>For examining the feasibility of treatment with CBT-TBI, descriptive analyses will be conducted to assess participants' retention/completion rates across study visits.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility - drop out rates</measure>
    <time_frame>12 weeks</time_frame>
    <description>For examining the feasibility of treatment with CBT-TBI, descriptive analyses will be conducted to assess participants' drop-out rates across study visits.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility - randomization, recruitment rates</measure>
    <time_frame>12 weeks</time_frame>
    <description>For examining the feasibility of treatment with CBT-TBI, descriptive analyses will be conducted to assess rate of recruitment and randomization (number randomized/number consented).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acceptability - satisfaction with treatment</measure>
    <time_frame>12 weeks</time_frame>
    <description>Descriptive analyses will be conducted to assess participants' satisfaction with CBT-TBI (Satisfaction with Therapy and Therapist Scale - Revised).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy - Treatment Response [Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)] (Exploratory Aim)</measure>
    <time_frame>12 weeks</time_frame>
    <description>The IDS-C is a 30-item clinician rated scale that assesses severity of depression. Scores range from 0 to 84, with higher scores indicative of greater depression severity.&#xD;
Descriptive analyses will be performed for percentage of responders (defined as 50% improvement on the IDS-C total) and remitters (≤6 on IDS-C total) at the end of treatment. The percent of responders and remitters in each group will be computed in order to estimate an effect size for a larger trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy - Treatment Response [Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)] (Exploratory Aim)</measure>
    <time_frame>12 weeks</time_frame>
    <description>The IDS-C is a 30-item clinician rated scale that assesses severity of depression. Scores range from 0 to 84, with higher scores indicative of greater depression severity.&#xD;
Change in depressive severity (IDS-C total) scores from baseline to post-treatment will also be analyzed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Traumatic Brain Injury</condition>
  <arm_group>
    <arm_group_label>Active Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who are randomized to begin the Cognitive Behavioral Therapy for individuals with TBI immediately after screening. This treatment is a version of Cognitive Behavioral Therapy (CBT) adapted specifically for patients who have experienced a moderate to severe Traumatic Brain Injury (TBI).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Waitlist Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants who are randomized to be put on a waitlist after screening. After 12 weeks of being on the waitlist, participants will be offered the Cognitive Behavioral Therapy for individuals with TBI</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive Behavioral Therapy for individuals with TBI</intervention_name>
    <description>Cognitive Behavioral Therapy for depression that has been adapted for a population who has experienced a moderate to severe Traumatic Brain Injury. This is a 12 week long treatment for depression with weekly visits that challenges negative thoughts and behaviors. This version has been specifically developed for the study to account for specific cognitive needs of individuals who have experienced a moderate to severe TBI.</description>
    <arm_group_label>Active Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Waitlist Control</intervention_name>
    <description>Participants will be randomized to a waitlist. They will attend biweekly study sessions for 12 weeks to track progress, but will receive their treatment as usual.</description>
    <arm_group_label>Waitlist Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults aged 18 and older&#xD;
&#xD;
          2. English language proficiency&#xD;
&#xD;
          3. Ability to provide written, informed consent; OR consent provided by legally&#xD;
             authorized representative with assent from subject&#xD;
&#xD;
          4. Ability to see and hear (hearing or visual loss cannot impair ADLs or in-room&#xD;
             conversation)&#xD;
&#xD;
          5. Has access to a smartphone/tablet/computer with internet and video capabilities for&#xD;
             virtual sessions&#xD;
&#xD;
          6. Having been hospitalized for moderate to severe TBI that occurred at least 3 months&#xD;
             prior to study entry&#xD;
&#xD;
          7. Meeting ANY ONE of the following severity criteria, as documented in electronic&#xD;
             medical record (EPIC) or available outside records:&#xD;
&#xD;
               1. GCS 3-12 with GCS motor score ≤ 5 within 4 hours after injury&#xD;
&#xD;
               2. GCS 3-12 with GCS motor score =6 within 4 hours after injury AND documented&#xD;
                  intracranial abnormalities on imaging&#xD;
&#xD;
               3. GCS 13-15 within 4 hours after injury AND documented intracranial abnormalities&#xD;
                  on imaging&#xD;
&#xD;
               4. Loss of consciousness (LOC) &gt; 30 min.&#xD;
&#xD;
               5. Post-traumatic amnesia (PTA) &gt; 24 hours&#xD;
&#xD;
          8. Out of PTA at the time of enrollment (GOAT&gt;75)&#xD;
&#xD;
          9. Clinically significant depressive symptoms: meets criteria for Major Depressive&#xD;
             Episode on the MINI or has a total score ≥ 23 on the Inventory of Depressive&#xD;
             Symptomatology - Clinician rated (IDS-C)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Uncontrolled medical illness&#xD;
&#xD;
          2. Behavioral dyscontrol, defined as the presence of verbally or physically aggressive&#xD;
             behavior in the past month, as evidenced in medical records, pre-screening interviews,&#xD;
             or observed by any study staff&#xD;
&#xD;
          3. Presents with PTSD as the primary diagnosis, as determined by a clinician&#xD;
&#xD;
          4. Substance use disorder, moderate or severe, within the past 6 months&#xD;
&#xD;
          5. Has bipolar disorder, a primary psychotic disorder or current psychotic symptoms, or&#xD;
             acute suicidality or homicidality&#xD;
&#xD;
          6. Currently receiving regular (≥ 2 times/ mo.) psychosocial treatment for depression&#xD;
&#xD;
          7. Has participated in CBT for depression within the past 6 months&#xD;
&#xD;
          8. Individuals with history of dementia or severe cognitive impairment that is not&#xD;
             related to TBI (e.g., cognitive impairment requiring assistance with basic activities&#xD;
             of daily living, such as getting ready in the morning)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lauren B Fisher, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 4, 2017</study_first_submitted>
  <study_first_submitted_qc>October 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Lauren Fisher</investigator_full_name>
    <investigator_title>Clinical Psychologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 14, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03307070/Prot_004.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 7, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03307070/SAP_005.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/NCT03307070
org study id: 2016P002823
nct id: NCT03307070
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Cognitive behavioral therapy for major depressive disorder (MDD) was adapted for individuals
      with moderate to severe traumatic brain injury (TBI) (CBT-TBI). A structured, treatment
      manual was developed.

      The primary aim is to evaluate the acceptability and tolerability of, and adherence to,
      CBT-TBI in a randomized waitlist-controlled, 12-week pilot trial (N=40).

      The exploratory aim is to evaluate the potential efficacy of CBT-TBI for MDD in the
      randomized pilot trial (N=40) and possible moderators and mediators of outcome.
The primary aim of this study is to develop a highly acceptable, manualized treatment
      (CBT-TBI) for MDD in patients with moderate to severe TBI. Initial feasibility data from a
      small, open pilot will inform the randomized controlled trial. Primary analyses will examine
      feasibility and acceptability of the intervention. The investigators will then pilot test the
      efficacy of the intervention to reduce depressive symptoms (IDS-C) after 12 weeks compared to
      a waitlist control group.

      The proposed study involves the following points of contact: (1) Obtaining informed consent
      and screening (may be broken up into multiple visits), (2) biweekly clinician assessments of
      depressive and neuropsychiatric symptoms (weeks 2, 4, 6, 8, 10), (3) weekly self-report
      assessments of depressive symptoms for those receiving the intervention, (4) 12 weekly
      individual CBT-TBI sessions for those randomized to the intervention, (5) a comprehensive
      assessment at week 12 (primary endpoint), which includes the neuropsychological battery, and
      (6) a 3-month follow-up assessment for those who received the intervention. The week 12 visit
      can be split into two parts, with the neuropsychological assessment occurring during the
      second part, in order to accommodate subjects' potential limitations due to fatigue.
      Procedures for this study were all conducted remotely after March 17, 2020.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study is a randomized, waitlist controlled trial. All participants randomized to waitlist were offered the opportunity to receive the intervention after completion of the waitlist.
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility - retention/completion rates
time frame: 12 weeks
description: For examining the feasibility of treatment with CBT-TBI, descriptive analyses will be conducted to assess participants' retention/completion rates across study visits.
measure: Feasibility - drop out rates
time frame: 12 weeks
description: For examining the feasibility of treatment with CBT-TBI, descriptive analyses will be conducted to assess participants' drop-out rates across study visits.
measure: Feasibility - randomization, recruitment rates
time frame: 12 weeks
description: For examining the feasibility of treatment with CBT-TBI, descriptive analyses will be conducted to assess rate of recruitment and randomization (number randomized/number consented).
measure: Acceptability - satisfaction with treatment
time frame: 12 weeks
description: Descriptive analyses will be conducted to assess participants' satisfaction with CBT-TBI (Satisfaction with Therapy and Therapist Scale - Revised).
measure: Efficacy - Treatment Response [Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)] (Exploratory Aim)
time frame: 12 weeks
description: The IDS-C is a 30-item clinician rated scale that assesses severity of depression. Scores range from 0 to 84, with higher scores indicative of greater depression severity.
Descriptive analyses will be performed for percentage of responders (defined as 50% improvement on the IDS-C total) and remitters (≤6 on IDS-C total) at the end of treatment. The percent of responders and remitters in each group will be computed in order to estimate an effect size for a larger trial.
measure: Efficacy - Treatment Response [Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)] (Exploratory Aim)
time frame: 12 weeks
description: The IDS-C is a 30-item clinician rated scale that assesses severity of depression. Scores range from 0 to 84, with higher scores indicative of greater depression severity.
Change in depressive severity (IDS-C total) scores from baseline to post-treatment will also be analyzed.
arm group label: Active Group
arm group type: Active Comparator
description: Participants who are randomized to begin the Cognitive Behavioral Therapy for individuals with TBI immediately after screening. This treatment is a version of Cognitive Behavioral Therapy (CBT) adapted specifically for patients who have experienced a moderate to severe Traumatic Brain Injury (TBI).
arm group label: Waitlist Control
arm group type: Other
description: Participants who are randomized to be put on a waitlist after screening. After 12 weeks of being on the waitlist, participants will be offered the Cognitive Behavioral Therapy for individuals with TBI
intervention type: Behavioral
intervention name: Cognitive Behavioral Therapy for individuals with TBI
description: Cognitive Behavioral Therapy for depression that has been adapted for a population who has experienced a moderate to severe Traumatic Brain Injury. This is a 12 week long treatment for depression with weekly visits that challenges negative thoughts and behaviors. This version has been specifically developed for the study to account for specific cognitive needs of individuals who have experienced a moderate to severe TBI.
arm group label: Active Group
intervention type: Other
intervention name: Waitlist Control
description: Participants will be randomized to a waitlist. They will attend biweekly study sessions for 12 weeks to track progress, but will receive their treatment as usual.
arm group label: Waitlist Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lauren B Fisher, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Lauren Fisher
investigator title: Clinical Psychologist
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Wounds and Injuries
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
provided document: 
provided document: 