<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/NCT03275571</url>
  </required_header>
  <id_info>
    <org_study_id>2018-3508</org_study_id>
    <nct_id>NCT03275571</nct_id>
  </id_info>
  <brief_title>HIV, Computerized Depression Therapy &amp; Cognition</brief_title>
  <official_title>The Effects of Computerized Cognitive Behavior Therapy (cCBT) on Brain Health: A Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Among people with HIV, the severity of depressive symptoms has repeatedly been associated&#xD;
      with the presence of self-reported cognitive difficulties, even in the absence of impairment&#xD;
      on neuropsychological testing. There is uncertainty about the clinical importance of these&#xD;
      self-reports, especially when neuropsychological testing is normal.&#xD;
&#xD;
      However, there is growing evidence that these self-reports are clinically important. For&#xD;
      example, among patients with major depressive disorder (MDD), evidence suggests that&#xD;
      functional impairments is mediated by self-reported cognitive dysfunction, rather than&#xD;
      objective cognitive dysfunction. Treatment of depression with Cognitive-Behaviour Therapy&#xD;
      (CBT) has been shown to improve depressive symptoms and psychosocial functioning in patients&#xD;
      with recurrent major depressive disorder, but there are few studies of the impact of&#xD;
      psychotherapy on self-reported cognition and cognitive performance. Good Days Ahead (GDA) is&#xD;
      a computerized treatment program developed to address symptoms of depression and anxiety. It&#xD;
      teaches the basic principles of computerized behavioral therapy (CBT) in nine therapy&#xD;
      sessions, each typically taking 30 minutes to complete. GDA has been found to be as effective&#xD;
      as face-to-face CBT in decreasing symptoms of depression and anxiety.&#xD;
&#xD;
      The hypothesis is that people whose depressive symptoms are reduced following treatment with&#xD;
      cCBT will also report fewer cognitive difficulties than before treatment. A second hypothesis&#xD;
      is that changes in self-reported cognition will be concordant with changes in cognitive&#xD;
      performance, such that people who make no improvement in self-report cognition will also show&#xD;
      no improvement in cognitive performance and those who do improve on self-report will improve&#xD;
      on cognitive performance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Among people with HIV, the severity of depressive symptoms has repeatedly been associated&#xD;
      with the presence of self-reported cognitive difficulties, even in the absence of impairment&#xD;
      on neuropsychological testing. There is uncertainty about the clinical importance of these&#xD;
      self-reports, especially when neuropsychological testing is normal, as they are thought to be&#xD;
      susceptible to patients' biases and insights into their illness.&#xD;
&#xD;
      However, there is growing evidence that these self-reports are clinically important. Among&#xD;
      patients with major depressive disorder (MDD), evidence suggests that functional impairments&#xD;
      is mediated by self-reported cognitive dysfunction, rather than objective cognitive&#xD;
      dysfunction. For example, Buist-Bouwman et al reported that more than one-quarter of the&#xD;
      impact of MDD on work loss was directly attributable to self-reported cognitive difficulties&#xD;
      and that cognition was a significant mediator of the association between MDD and work or role&#xD;
      dysfunction.&#xD;
&#xD;
      When depression is treated with antidepressant medication, some degree of improvement on&#xD;
      neuropsychological tests has been documented. However, many studies have evaluated cognitive&#xD;
      outcomes before and after treatment rather than comparing them with placebo, potentially&#xD;
      biasing the results by learning effects, which limits the strength of the conclusions that&#xD;
      can be drawn.&#xD;
&#xD;
      Treatment of depression with Cognitive-Behaviour Therapy (CBT) has been shown to improve&#xD;
      depressive symptoms and psychosocial functioning in patients with recurrent major depressive&#xD;
      disorder, but there are few studies of the impact of psychotherapy on self-reported cognition&#xD;
      and cognitive performance. In a group of patients with highly recurrent depression (≥4&#xD;
      episodes) over 2 years of follow-up, Conradi et al showed that those randomized to receive&#xD;
      psycho-education plus CBT reported the presence of cognitive symptoms significantly less of&#xD;
      the time compared to those receiving psycho-education only (15% of the time or 3.6 months&#xD;
      compared to 47% or 11.3 months).&#xD;
&#xD;
      In the HIV population, a single study has examined the effect of treatment of depression on&#xD;
      self-reported cognitive difficulties and performance on neuropsychological tests, as part of&#xD;
      a randomized controlled trial of antidepressant efficacy. Following 12 weeks of&#xD;
      antidepressant treatment, HIV+ individuals who reported a decrease in depressive symptoms&#xD;
      also reported significantly fewer cognitive difficulties, despite an absence of improvement&#xD;
      on neuropsychological testing.&#xD;
&#xD;
      In the context where the use of questionnaires eliciting cognitive difficulties is suggested&#xD;
      as a first-line screening for HIV-Associated Neurocognitive Disorder, it is important to&#xD;
      document the clinical factors that influence these self-reports in order to inform their&#xD;
      clinical interpretation and develop interventions for individuals reporting cognitive&#xD;
      difficulties.&#xD;
&#xD;
      Understanding and Optimizing Brain Health Now (BHN) cohort study: Cohort participants (N=840)&#xD;
      are studied prospectively over a 27-month period with visits every 9 months. Patients&#xD;
      complete questionnaires on mood (Hospital Anxiety Depression Scale-HADS), presence of&#xD;
      cognitive symptoms (Patient Deficit Questionnaire-PDQ), and a computer-based evaluation of&#xD;
      cognitive ability (B-CAM).&#xD;
&#xD;
      Computerized Cognitive-Behavioral Therapy (cCBT): A number of computerized treatment programs&#xD;
      have been developed to address symptoms of depression and anxiety, and several meta-analyses&#xD;
      of randomized controlled trials (RCTs) have shown evidence for their effectiveness. One such&#xD;
      program, Good Days Ahead, teaches the basic principles of CBT in nine therapy sessions, each&#xD;
      typically taking 30 minutes to complete. Good Days Ahead has been found to be as effective as&#xD;
      face-to-face CBT in decreasing symptoms of depression and anxiety. Patients receiving&#xD;
      treatment delivered by a computer can be provided with different levels of guidance and&#xD;
      support: self-guidance, guidance by a technician who sends reminders, or guidance by a&#xD;
      clinician. A recent meta-analysis of cCBT for depression and anxiety has shown that the&#xD;
      treatment delivered with no guidance or support yielded, on average, a smaller effect size&#xD;
      (Cohen's d = 0.17) than cCBT delivered with at least one hour of knowledgeable assistance&#xD;
      during the course of therapy (Cohen's d = 0.72). Offering some assistance thus appears to be&#xD;
      necessary for achieving better therapy outcomes.&#xD;
&#xD;
      Study Design : This study is part of a larger project based upon a cohort multiple randomized&#xD;
      controlled design. Within a fully characterized cohort followed over time (n=840), people&#xD;
      meeting the specific criteria for one or more interventions (here cCBT) are identified and a&#xD;
      sample is randomly selected to receive the intervention. When the intervention is under&#xD;
      investigation, the remaining eligible persons who do not receive the intervention serve as&#xD;
      controls. In this study, we are not testing the effectiveness of cCBT as this has been&#xD;
      demonstrated. Rather the researchers are focusing on changes in cognition in relation to&#xD;
      depressive symptoms mediated by cCBT. This study is an exploration of a hypothesis using a&#xD;
      single cohort design with two repeated measures. For exploratory studies, an N of 30&#xD;
      optimizes an analysis based on means under the central limit theorem.&#xD;
&#xD;
      Intervention: Participants who are eligible will receive online access to the Good Days Ahead&#xD;
      cCBT program. Good Days Ahead is a learning module based on scientifically proven,&#xD;
      evidence-based techniques. The program's content follows the teachings of the basic&#xD;
      principles of CBT. The underlying platform generates customized learning experiences for each&#xD;
      individual user with content including videos, text, quizzes and interactive exercises. The&#xD;
      program comprises nine lessons of 30 minute each during which the user first learns the key&#xD;
      concepts; then applies them to the program's main character who suffers from depression; and&#xD;
      then applies those techniques to their own personal challenges&#xD;
      (http://www.empower-interactive.com/solutions/good-days-ahead). Participants are expected to&#xD;
      complete the nine sessions over 9-12 weeks.&#xD;
&#xD;
      As patients complete the cCBT program, their progress will be monitored by the research&#xD;
      coordinator through a secure web site, using the program's dashboard feature that includes&#xD;
      tracking of mood ratings, exercises, comprehension and completion rates. Participants will&#xD;
      receive guidance during regular contacts by a trained research coordinator knowledgeable&#xD;
      about the program and the basics of CBT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low recruitment rate, parent study has ended&#xD;
  </why_stopped>
  <start_date type="Actual">September 6, 2017</start_date>
  <completion_date type="Actual">August 13, 2019</completion_date>
  <primary_completion_date type="Actual">August 13, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Self-reported cognitive difficulties (C3Q)</measure>
    <time_frame>One week before the beginning of the intervention and up to 4 weeks after the end of the intervention</time_frame>
    <description>The Communicating Cognitive Concerns Questionnaire evaluated cognitive concerns participants may have.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Depressive symptoms measure (HADS)</measure>
    <time_frame>One week before the beginning of the intervention and up to 4 weeks after the end of the intervention</time_frame>
    <description>The Hospital Anxiety and Depression Scale is a two 7-items scale designed to rate depression and anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Performance measure (B-CAM)</measure>
    <time_frame>Up to 9 months before the beginning of the intervention and up to 2 months after the end of the intervention.</time_frame>
    <description>The research team will be looking at changes on the B-CAM (brief cognitive ability measure)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>HIV Infections</condition>
  <condition>Depression</condition>
  <condition>CBT</condition>
  <arm_group>
    <arm_group_label>cCBT intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the course of 9 weeks, 30 min online sessions, once per week, with a fictive therapist.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>cCBT intervention</intervention_name>
    <description>During each 30 minutes sessions, the participants will learn key concepts on depression, then will apply them to the program's main character who suffers from depression, and then will apply those techniques to their own personal challenges.</description>
    <arm_group_label>cCBT intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants in the cohort study &quot;Understanding and Optimizing Brain Health in HIV&#xD;
             Now&quot; with at least one remaining visit&#xD;
&#xD;
          -  Able to communicate (understand and read) in English&#xD;
&#xD;
          -  Depression subscale of the HADS (HADS-D) ≥ 8&#xD;
&#xD;
          -  Presence of self-reported cognitive difficulties (PDQ) &gt;40&#xD;
&#xD;
          -  Score on the B-CAM &gt; 14&#xD;
&#xD;
          -  Willing to undergo 9 sessions of cCBT as per instructions and to have weekly contact&#xD;
             with a research coordinator from the central site (by email or phone)&#xD;
&#xD;
          -  Access to the internet&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        • Current use of street drugs (excluding marijuana)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie-Josee Brouillette, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lesley Fellows, MD/DPhil</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McGill University Health Center</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 6, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>September 3, 2019</last_update_submitted>
  <last_update_submitted_qc>September 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McGill University</investigator_affiliation>
    <investigator_full_name>Marie-Josée Brouillette</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Cognition</keyword>
  <keyword>Intervention</keyword>
  <keyword>Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT03275571/Prot_SAP_000.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/NCT03275571
org study id: 2018-3508
nct id: NCT03275571
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Among people with HIV, the severity of depressive symptoms has repeatedly been associated
      with the presence of self-reported cognitive difficulties, even in the absence of impairment
      on neuropsychological testing. There is uncertainty about the clinical importance of these
      self-reports, especially when neuropsychological testing is normal.

      However, there is growing evidence that these self-reports are clinically important. For
      example, among patients with major depressive disorder (MDD), evidence suggests that
      functional impairments is mediated by self-reported cognitive dysfunction, rather than
      objective cognitive dysfunction. Treatment of depression with Cognitive-Behaviour Therapy
      (CBT) has been shown to improve depressive symptoms and psychosocial functioning in patients
      with recurrent major depressive disorder, but there are few studies of the impact of
      psychotherapy on self-reported cognition and cognitive performance. Good Days Ahead (GDA) is
      a computerized treatment program developed to address symptoms of depression and anxiety. It
      teaches the basic principles of computerized behavioral therapy (CBT) in nine therapy
      sessions, each typically taking 30 minutes to complete. GDA has been found to be as effective
      as face-to-face CBT in decreasing symptoms of depression and anxiety.

      The hypothesis is that people whose depressive symptoms are reduced following treatment with
      cCBT will also report fewer cognitive difficulties than before treatment. A second hypothesis
      is that changes in self-reported cognition will be concordant with changes in cognitive
      performance, such that people who make no improvement in self-report cognition will also show
      no improvement in cognitive performance and those who do improve on self-report will improve
      on cognitive performance.
Among people with HIV, the severity of depressive symptoms has repeatedly been associated
      with the presence of self-reported cognitive difficulties, even in the absence of impairment
      on neuropsychological testing. There is uncertainty about the clinical importance of these
      self-reports, especially when neuropsychological testing is normal, as they are thought to be
      susceptible to patients' biases and insights into their illness.

      However, there is growing evidence that these self-reports are clinically important. Among
      patients with major depressive disorder (MDD), evidence suggests that functional impairments
      is mediated by self-reported cognitive dysfunction, rather than objective cognitive
      dysfunction. For example, Buist-Bouwman et al reported that more than one-quarter of the
      impact of MDD on work loss was directly attributable to self-reported cognitive difficulties
      and that cognition was a significant mediator of the association between MDD and work or role
      dysfunction.

      When depression is treated with antidepressant medication, some degree of improvement on
      neuropsychological tests has been documented. However, many studies have evaluated cognitive
      outcomes before and after treatment rather than comparing them with placebo, potentially
      biasing the results by learning effects, which limits the strength of the conclusions that
      can be drawn.

      Treatment of depression with Cognitive-Behaviour Therapy (CBT) has been shown to improve
      depressive symptoms and psychosocial functioning in patients with recurrent major depressive
      disorder, but there are few studies of the impact of psychotherapy on self-reported cognition
      and cognitive performance. In a group of patients with highly recurrent depression (≥4
      episodes) over 2 years of follow-up, Conradi et al showed that those randomized to receive
      psycho-education plus CBT reported the presence of cognitive symptoms significantly less of
      the time compared to those receiving psycho-education only (15% of the time or 3.6 months
      compared to 47% or 11.3 months).

      In the HIV population, a single study has examined the effect of treatment of depression on
      self-reported cognitive difficulties and performance on neuropsychological tests, as part of
      a randomized controlled trial of antidepressant efficacy. Following 12 weeks of
      antidepressant treatment, HIV+ individuals who reported a decrease in depressive symptoms
      also reported significantly fewer cognitive difficulties, despite an absence of improvement
      on neuropsychological testing.

      In the context where the use of questionnaires eliciting cognitive difficulties is suggested
      as a first-line screening for HIV-Associated Neurocognitive Disorder, it is important to
      document the clinical factors that influence these self-reports in order to inform their
      clinical interpretation and develop interventions for individuals reporting cognitive
      difficulties.

      Understanding and Optimizing Brain Health Now (BHN) cohort study: Cohort participants (N=840)
      are studied prospectively over a 27-month period with visits every 9 months. Patients
      complete questionnaires on mood (Hospital Anxiety Depression Scale-HADS), presence of
      cognitive symptoms (Patient Deficit Questionnaire-PDQ), and a computer-based evaluation of
      cognitive ability (B-CAM).

      Computerized Cognitive-Behavioral Therapy (cCBT): A number of computerized treatment programs
      have been developed to address symptoms of depression and anxiety, and several meta-analyses
      of randomized controlled trials (RCTs) have shown evidence for their effectiveness. One such
      program, Good Days Ahead, teaches the basic principles of CBT in nine therapy sessions, each
      typically taking 30 minutes to complete. Good Days Ahead has been found to be as effective as
      face-to-face CBT in decreasing symptoms of depression and anxiety. Patients receiving
      treatment delivered by a computer can be provided with different levels of guidance and
      support: self-guidance, guidance by a technician who sends reminders, or guidance by a
      clinician. A recent meta-analysis of cCBT for depression and anxiety has shown that the
      treatment delivered with no guidance or support yielded, on average, a smaller effect size
      (Cohen's d = 0.17) than cCBT delivered with at least one hour of knowledgeable assistance
      during the course of therapy (Cohen's d = 0.72). Offering some assistance thus appears to be
      necessary for achieving better therapy outcomes.

      Study Design : This study is part of a larger project based upon a cohort multiple randomized
      controlled design. Within a fully characterized cohort followed over time (n=840), people
      meeting the specific criteria for one or more interventions (here cCBT) are identified and a
      sample is randomly selected to receive the intervention. When the intervention is under
      investigation, the remaining eligible persons who do not receive the intervention serve as
      controls. In this study, we are not testing the effectiveness of cCBT as this has been
      demonstrated. Rather the researchers are focusing on changes in cognition in relation to
      depressive symptoms mediated by cCBT. This study is an exploration of a hypothesis using a
      single cohort design with two repeated measures. For exploratory studies, an N of 30
      optimizes an analysis based on means under the central limit theorem.

      Intervention: Participants who are eligible will receive online access to the Good Days Ahead
      cCBT program. Good Days Ahead is a learning module based on scientifically proven,
      evidence-based techniques. The program's content follows the teachings of the basic
      principles of CBT. The underlying platform generates customized learning experiences for each
      individual user with content including videos, text, quizzes and interactive exercises. The
      program comprises nine lessons of 30 minute each during which the user first learns the key
      concepts; then applies them to the program's main character who suffers from depression; and
      then applies those techniques to their own personal challenges
      (http://www.empower-interactive.com/solutions/good-days-ahead). Participants are expected to
      complete the nine sessions over 9-12 weeks.

      As patients complete the cCBT program, their progress will be monitored by the research
      coordinator through a secure web site, using the program's dashboard feature that includes
      tracking of mood ratings, exercises, comprehension and completion rates. Participants will
      receive guidance during regular contacts by a trained research coordinator knowledgeable
      about the program and the basics of CBT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Self-reported cognitive difficulties (C3Q)
time frame: One week before the beginning of the intervention and up to 4 weeks after the end of the intervention
description: The Communicating Cognitive Concerns Questionnaire evaluated cognitive concerns participants may have.
measure: Depressive symptoms measure (HADS)
time frame: One week before the beginning of the intervention and up to 4 weeks after the end of the intervention
description: The Hospital Anxiety and Depression Scale is a two 7-items scale designed to rate depression and anxiety.
measure: Cognitive Performance measure (B-CAM)
time frame: Up to 9 months before the beginning of the intervention and up to 2 months after the end of the intervention.
description: The research team will be looking at changes on the B-CAM (brief cognitive ability measure)
arm group label: cCBT intervention
arm group type: Experimental
description: Over the course of 9 weeks, 30 min online sessions, once per week, with a fictive therapist.
intervention type: Behavioral
intervention name: cCBT intervention
description: During each 30 minutes sessions, the participants will learn key concepts on depression, then will apply them to the program's main character who suffers from depression, and then will apply those techniques to their own personal challenges.
arm group label: cCBT intervention
criteria: 
gender: All
minimum age: 35 Years
maximum age: N/A
healthy volunteers: No
last name: Marie-Josee Brouillette, MD
role: Principal Investigator
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Lesley Fellows, MD/DPhil
role: Principal Investigator
affiliation: McGill University
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: McGill University
investigator full name: Marie-Josée Brouillette
investigator title: Associate Professor
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: No
provided document: 