xml: <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/NCT06001346</url>
    </required_header>
    <id_info>
      <org_study_id>1R61MH129407</org_study_id>
      <secondary_id>1R61MH129407-01A1</secondary_id>
      <nct_id>NCT06001346</nct_id>
    </id_info>
    <brief_title>CBT+ for Depression</brief_title>
    <acronym>CBT+</acronym>
    <official_title>ActiveCBT for Depression: Transforming Treatment Through Exercise Priming</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Iowa State University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute of Mental Health (NIMH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Iowa 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>
        This study investigates the effects of a novel intervention approach, intentionally&#xD;
        sequencing aerobic exercise immediately prior to therapy sessions (i.e., cognitive behavioral&#xD;
        therapy [CBT]) to determine its effects on both specific and common factors underlying the&#xD;
        antidepressant effect of CBT (i.e., mechanisms of CBT). To assess the utility of this&#xD;
        treatment augmentation, investigators plan to conduct a randomized controlled trial involving&#xD;
        40 adults with Major Depressive Disorder who will watch a nature documentary while either&#xD;
        resting quietly (termed 'CalmCBT') or exercising at a moderate intensity ('ActiveCBT')&#xD;
        immediately prior to 8 weekly sessions of CBT. It is hypothesized that target CBT mechanisms&#xD;
        of antidepressant action (i.e., self-reported working alliance and behavioral activation)&#xD;
        will be more effectively engaged by ActiveCBT vs. CalmCBT.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Frontline treatments for major depressive disorder (MDD), including cognitive behavioral&#xD;
        therapy (CBT), have limited effectiveness, with half of patients not responding to CBT and&#xD;
        half relapsing within 2 years. Strategies that increase the potency of MDD treatments are&#xD;
        needed. We are testing a novel treatment strategy using aerobic exercise to prime a&#xD;
        subsequent CBT session ('ActiveCBT'). Exercise priming is hypothesized to lead to greater&#xD;
        engagement of CBT mechanisms of action through both common and specific factors linked to&#xD;
        depression outcomes; this CBT augmentation approach has yet to be empirically tested. The&#xD;
        study will consist of an 8-week randomized controlled trial in 40 adults with MDD performing&#xD;
        30-minutes of moderate exercise or quiet rest (CalmCBT vs. ActiveCBT) prior to weekly CBT&#xD;
        sessions. Using a time- and attention-matched control, all participants will view a&#xD;
        standardized documentary series for these 30 pre-therapy minutes with the only difference&#xD;
        between groups being exercise or calmly resting. This project will also employ machine&#xD;
        learning and natural language processing via the Lyssn platform to objectively evaluate the&#xD;
        language and words used during therapy. The overall goals are to: 1) demonstrate exercise&#xD;
        priming effects on target CBT mechanisms, 2) link psychological and neuroplastic exercise&#xD;
        priming to CBT mechanisms, and 3) explore the sensitivity of objective machine learning-based&#xD;
        markers from Lyssn to ActiveCBT-induced therapy differences. This trial will establish the&#xD;
        potential for a subsequent confirmatory efficacy trial to rigorously test the potential of&#xD;
        exercise priming to enhance treatment. If this innovative, biologically-informed approach&#xD;
        successfully 'primes' subsequent therapy, this could be used to augment other treatments and&#xD;
        in other disorders, significantly improving mental health treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2025</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>Double (Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Average self-reported working alliance measured by Working Alliance Inventory (WAI)</measure>
      <time_frame>Weeks 1-8 CBT+ visits</time_frame>
      <description>Working Alliance Inventory-Short Revised (WAI) is a 12-item survey on experiences over a therapy session and connection with a therapist. It consists of three subscales: tasks, goals, and therapist-client bond. The Goal, Task, and Bond domains each have scores ranging from 5 to 20. Higher scores indicate a better therapeutic alliance.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Average change in self-reported behavioral activation measured by Behavioral Activation for Depression Scale (BADS)</measure>
      <time_frame>Intake, Weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up</time_frame>
      <description>The Behavioral Activation for Depression Scale (BADS) will be used to assess changes in behavioral activity. The scale is designed to be administered weekly to measure changes over the course of Behavioral Activation for depression. It consists of 25 questions that inquire about Activation, Avoidance/Rumination, Work/School Impairment, and Social Impairment (sub-scaled). A total score (all subscales summed) will be used as a primary outcome in this study.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes in clinician-rated depression symptoms measured by GRID-Hamilton Depression Rating Scale (GRID-HAM-D)</measure>
      <time_frame>Intake, final, 12-week follow up, 1-year follow up</time_frame>
      <description>The GRID-HAM-D is a clinician-completed questionnaire that will be used to rate depressive symptom severity. The questionnaire is designed for adults and is used to rate the intensity and frequency of depressive symptoms by probing mood, feelings of guilt, suicidal ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. As recommended by the Depression Rating Scale Standardization Team, Clinical Interviewers will follow the Structured Interview Guide and use GRID scoring, in which dimensions of intensity and frequency of a symptom are rated independently for each item. Higher scores reflect greater symptom severity, categorized as Normal (0-7), Mild Depression (8-13), Moderate Depression (14-18), Severe Depression (19-22), and Very Severe Depression (&gt;23).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in self-reported depression symptoms measured by Patient Health Questionnaire-9 (PHQ-9)</measure>
      <time_frame>Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up</time_frame>
      <description>The Patient Health Questionnaire-9 (PHQ-9) is a 9-question self-report instrument used to assess presence and severity of depressive symptoms, with scores categorized 0-4, 5-9, 10-14, 15-19, and 20-27 as minimal, mild, moderate, moderately severe, and severe depression, respectively.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in MDD diagnosis measured by Structured Clinical Interview for DSM-5 Disorders (SCID)</measure>
      <time_frame>Intake, final, 12-week follow up, 1-year follow up</time_frame>
      <description>The SCID is a clinician-administered semi-structured interview guide for making diagnoses according to the diagnostic criteria published in the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5). It provides diagnoses for depressive and bipolar disorders, schizophrenia spectrum and other psychotic disorders, substance use disorders, anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder),obsessive-compulsive disorder, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and adjustment disorder.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in suicidal thoughts measured by the Columbia-Suicide Severity Rating Scale (CSSRS)</measure>
      <time_frame>Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up</time_frame>
      <description>The C-SSRS will be used to assess and monitor suicide ideation and behavior. The severity of the ideation subscale is rated on a 5-point ordinal scale: 1 = wish to be dead, 2 = nonspecific active suicidal thoughts, 3 = suicidal thoughts with methods, 4 =suicidal intent, and 5 = suicidal intent with plan. Suicide behaviors are rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal,self-injurious behavior.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average anhedonia measured by Dimensional Anhedonia Rating Scale (DARS)</measure>
      <time_frame>Weeks 1-8 CBT+ visits (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]), final, 12-week follow up, 1-year follow up</time_frame>
      <description>The DARS is a self-report measure that assesses state anhedonia across multiple domains. DARS is a 17-item survey on state anhedonia divided into four domains: hobbies, food/drink, social activities, and sensory experiences. Subjects must list two activities within each of these categories that they consider their favorite and then respond to questions regarding their interest in/enjoyment of those activities on a 5-point Likert scale from &quot;Not at all&quot; to &quot;Very much.&quot; During pre/post-administration, participants will be asked to respond to how they are feeling &quot;right now.&quot;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average anhedonia measured by an Anhedonia Visual Analogue Scale (Anhedonia VAS)</measure>
      <time_frame>Weeks 1-8 CBT+ visits (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]), final, 12-week follow up, 1-year follow up</time_frame>
      <description>An anhedonia Visual Analog Scale [VAS] with 0 indicating 'No pleasure at all' and 100 indicating 'Greatest pleasure imaginable' will be used to measure anhedonia. In past research by the PI, correlations between the DARS and VAS were 0.49-0.69 indicating a moderate-to-strong agreement between the measures. The VAS will be used to provide a supplementary assessment of anhedonia.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum brain derived neurotrophic factor (BDNF)</measure>
      <time_frame>Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)</time_frame>
      <description>Serum BDNF will be quantified from a standard blood draw. Blood samples collected during Visits 1, 4, and 8 will be allowed to clot for 30 minutes and then centrifuged for ten minutes at 5500 RPM and 4 ◦C. Following centrifugation, blood serum will be extracted with samples stored at -80 ◦C until BDNF analysis. Enzyme-linked immunosorbent assay (ELISA) kits will measure the concentration of total BDNF in the serum according to the manufacturer's instructions. Each blood sample will be run in duplicate and averaged.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in monitor-assessed physical activity measured by accelerometry</measure>
      <time_frame>Intake, weeks 4 &amp; 8 CBT+ visits (monitors worn 1 week following each time point)</time_frame>
      <description>Participants will place an activPAL on the midline of the thigh on either leg and wear the monitor during all waking hours, removing it only for water-based activities (e.g., swimming). For data to be valid, the monitor must have been worn for 20 hours on at least 4 days, including a minimum of 3 weekdays and 1 weekend day. Sleep time will be parsed out from each day's sitting/lying time automatically using PALanalysis. From these data, average minutes of sitting per day will be used to assess total sedentary time, minutes of stepping time with a cadence ≥75 and &lt;100 will be used to assess minutes of light-intensity physical activity and minutes of stepping time with a cadence ≥100 will be used to assess minutes of moderate to vigorous physical activity (MVPA).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in self-reported physical activity measured by the International Physical Activity Questionnaire - Short Form (IPAQ-SF)</measure>
      <time_frame>Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up</time_frame>
      <description>The IPAQ is a physical activity questionnaire that inquires about average amounts of walking, moderate physical activity, vigorous physical activity, and sitting time per week.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in quality of life measured by the 36-Item Short Form Health Survey (SF-36)</measure>
      <time_frame>Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up</time_frame>
      <description>The SF-36 assesses health-related quality of life. It consists of eight scaled scores (including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher the score the less disability (i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in anxiety measured by Generalized Anxiety Disorder 7 (GAD-7)</measure>
      <time_frame>Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up</time_frame>
      <description>Generalized Anxiety Disorder 7 (GAD-7) is a self-reported questionnaire for measuring generalized anxiety disorder. GAD-7 has seven items, which measure the severity of various signs of GAD according to reported response categories of: Not at all (0 points), Several days (1 point), More than half the days (2 points), and Nearly every day (3 points), with scores of 5, 10, and 15 as cut-off points for mild, moderate and severe anxiety, respectively.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average automatic thoughts measured by Automatic Thoughts Questionnaire (ATQ)</measure>
      <time_frame>Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up</time_frame>
      <description>The ATQ is a 30-item instrument that measures the frequency of automatic negative statements about the self. Each item is rated on the frequency of an occurrence from &quot;not at all&quot; to &quot;all the time&quot;. Total scores are the sum of all 30 items, with higher totals indicating a higher level of automatic negative self-statements.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average session effectiveness measured by Session Evaluation Questionnaire (SEQ)</measure>
      <time_frame>Weeks 1-8 CBT+ visits</time_frame>
      <description>Session Evaluation Questionnaire (SEQ) will be used to evaluate session effectiveness. This includes responses to twenty-one items in a 7-point bipolar adjective format questionnaire to assess how the client feels about each CBT session. The questionnaire assesses session depth, smoothness, positivity, and arousal. An overall score of the average of the values across each subscale will be used in this study.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Average Lyssn generated scores</measure>
      <time_frame>Weeks 1-8 CBT+ visits</time_frame>
      <description>Lyssn is an AI-powered assessment platform for recording and managing session files, and all clinical interviews and therapy sessions will be recorded on the Lyssn platform. Lyssn will process the audio files from therapy sessions to generate session-level data regarding collaboration and empathy as metrics related to the primary client ratings of working alliance, as well as generating CTRS fidelity metrics which will be used in the ongoing supervision and fidelity monitoring of all sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nature Connectedness Index (NCI)</measure>
      <time_frame>Intake, Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)</time_frame>
      <description>The NCI consist of 6 questions pertaining to nature connectedness. Participants respond using a 7-point Likert scale, ranging from 1 (Strongly Disagree) to 7 (Strongly Agree), with higher scores indicating greater levels of nature connectedness.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Health History Questions</measure>
      <time_frame>Intake</time_frame>
      <description>Health history will be self-reported. In addition, participants will be asked to list their current medications.</description>
    </other_outcome>
    <other_outcome>
      <measure>Demographic Questionnaire</measure>
      <time_frame>Intake</time_frame>
      <description>Demographic characteristics including age, sex, race, education, marital status, occupational status, and household income will be recorded or measured to characterize the sample.</description>
    </other_outcome>
    <other_outcome>
      <measure>Adverse Childhood Experience Survey (ACES)</measure>
      <time_frame>Intake</time_frame>
      <description>The ACES consists of 16 questions pertaining to the respondents' first 18 years of life. Participants respond with yes or no regarding if a childhood adverse event occurred. Adverse events questions are grouped by categories. Participants are scored for each event category they are exposed to with scores ranging from 0 (unexposed) to 7 (exposed to all categories).</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Major Depressive Disorder</condition>
    <arm_group>
      <arm_group_label>ActiveCBT</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will complete a standardized 30-minute exercise session on a stationary bike prior to therapy. Participants will view one of 8 standardized 30-minute nature documentary videos while exercising.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CalmCBT</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will view one of 8 standardized 30-minute nature documentary videos while resting quietly prior to therapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>ActiveCBT</intervention_name>
      <description>Participants will complete a standardized 30-minute aerobic exercise session on a stationary bicycle prior to therapy. Supervised exercise sessions will consist of steady-state exercise at a moderate intensity corresponding to a '13' or 'somewhat hard' rating of perceived exertion. Continuous monitoring of heart rate, resistance/load, and RPE will occur throughout exercise. To closely match the groups, participants will also view 30-minute nature videos while exercising.</description>
      <arm_group_label>ActiveCBT</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>CalmCBT</intervention_name>
      <description>Participants will view one of 8 standardized 30-minute nature videos while resting quietly prior to therapy. These are emotionally neutral videos and will allow for participants in both groups to have the same amount of attention and contact time.</description>
      <arm_group_label>CalmCBT</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosed with DSM-5 MDD, confirmed via SCID.&#xD;
  &#xD;
            -  Having current depressive symptoms of at least mild severity defined by HAM-D rating&#xD;
               ≥8.&#xD;
  &#xD;
            -  Being between age 18 and 65.&#xD;
  &#xD;
            -  Either not engaging in any mental health treatment (e.g., medication, psychological,&#xD;
               or behavioral) OR on a stable mental health treatment regimen and willing to maintain&#xD;
               it for the length of the intervention.&#xD;
  &#xD;
            -  Willing and safe to exercise based on the Physical Activity Readiness Questionnaire.&#xD;
  &#xD;
            -  Being CBT-naïve (as defined by never undergoing structured CBT).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  currently pregnant, nursing, or planning to become pregnant,&#xD;
  &#xD;
            -  severe obesity (BMI=40)&#xD;
  &#xD;
            -  diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID&#xD;
  &#xD;
            -  diagnosed with current Substance Use Disorder, via the SCID&#xD;
  &#xD;
            -  pose an imminent risk of self-harm or harm to others, assessed via the C-SSRS&#xD;
  &#xD;
            -  exhibit behavioral disturbance (e.g., aggression, mild-moderate cognitive impairment)&#xD;
               that would significantly interfere with study participation, assessed by clinical&#xD;
               research personnel&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Jacob Meyer, PhD</last_name>
      <phone>515-294-1386</phone>
      <email>jdmeyer3@iastate.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Iowa State University</investigator_affiliation>
      <investigator_full_name>Jacob Meyer</investigator_full_name>
      <investigator_title>Associate Professor, Kinesiology</investigator_title>
    </responsible_party>
    <keyword>Exercise Priming</keyword>
    <keyword>Depression</keyword>
    <keyword>Cognitive Behavioral 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>
      <mesh_term>Depressive Disorder, Major</mesh_term>
    </condition_browse>
    <provided_document_section>
      <provided_document>
        <document_type>Informed Consent Form</document_type>
        <document_has_protocol>No</document_has_protocol>
        <document_has_icf>Yes</document_has_icf>
        <document_has_sap>No</document_has_sap>
        <document_date>July 25, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT06001346/ICF_000.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06001346
  org study id: 1R61MH129407
  secondary id: 1R61MH129407-01A1
  nct id: NCT06001346
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study investigates the effects of a novel intervention approach, intentionally
        sequencing aerobic exercise immediately prior to therapy sessions (i.e., cognitive behavioral
        therapy [CBT]) to determine its effects on both specific and common factors underlying the
        antidepressant effect of CBT (i.e., mechanisms of CBT). To assess the utility of this
        treatment augmentation, investigators plan to conduct a randomized controlled trial involving
        40 adults with Major Depressive Disorder who will watch a nature documentary while either
        resting quietly (termed 'CalmCBT') or exercising at a moderate intensity ('ActiveCBT')
        immediately prior to 8 weekly sessions of CBT. It is hypothesized that target CBT mechanisms
        of antidepressant action (i.e., self-reported working alliance and behavioral activation)
        will be more effectively engaged by ActiveCBT vs. CalmCBT.
  Frontline treatments for major depressive disorder (MDD), including cognitive behavioral
        therapy (CBT), have limited effectiveness, with half of patients not responding to CBT and
        half relapsing within 2 years. Strategies that increase the potency of MDD treatments are
        needed. We are testing a novel treatment strategy using aerobic exercise to prime a
        subsequent CBT session ('ActiveCBT'). Exercise priming is hypothesized to lead to greater
        engagement of CBT mechanisms of action through both common and specific factors linked to
        depression outcomes; this CBT augmentation approach has yet to be empirically tested. The
        study will consist of an 8-week randomized controlled trial in 40 adults with MDD performing
        30-minutes of moderate exercise or quiet rest (CalmCBT vs. ActiveCBT) prior to weekly CBT
        sessions. Using a time- and attention-matched control, all participants will view a
        standardized documentary series for these 30 pre-therapy minutes with the only difference
        between groups being exercise or calmly resting. This project will also employ machine
        learning and natural language processing via the Lyssn platform to objectively evaluate the
        language and words used during therapy. The overall goals are to: 1) demonstrate exercise
        priming effects on target CBT mechanisms, 2) link psychological and neuroplastic exercise
        priming to CBT mechanisms, and 3) explore the sensitivity of objective machine learning-based
        markers from Lyssn to ActiveCBT-induced therapy differences. This trial will establish the
        potential for a subsequent confirmatory efficacy trial to rigorously test the potential of
        exercise priming to enhance treatment. If this innovative, biologically-informed approach
        successfully 'primes' subsequent therapy, this could be used to augment other treatments and
        in other disorders, significantly improving mental health treatment.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Investigator, Outcomes Assessor)
  measure: Average self-reported working alliance measured by Working Alliance Inventory (WAI)
  time frame: Weeks 1-8 CBT+ visits
  description: Working Alliance Inventory-Short Revised (WAI) is a 12-item survey on experiences over a therapy session and connection with a therapist. It consists of three subscales: tasks, goals, and therapist-client bond. The Goal, Task, and Bond domains each have scores ranging from 5 to 20. Higher scores indicate a better therapeutic alliance.
  measure: Average change in self-reported behavioral activation measured by Behavioral Activation for Depression Scale (BADS)
  time frame: Intake, Weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
  description: The Behavioral Activation for Depression Scale (BADS) will be used to assess changes in behavioral activity. The scale is designed to be administered weekly to measure changes over the course of Behavioral Activation for depression. It consists of 25 questions that inquire about Activation, Avoidance/Rumination, Work/School Impairment, and Social Impairment (sub-scaled). A total score (all subscales summed) will be used as a primary outcome in this study.
  measure: Changes in clinician-rated depression symptoms measured by GRID-Hamilton Depression Rating Scale (GRID-HAM-D)
  time frame: Intake, final, 12-week follow up, 1-year follow up
  description: The GRID-HAM-D is a clinician-completed questionnaire that will be used to rate depressive symptom severity. The questionnaire is designed for adults and is used to rate the intensity and frequency of depressive symptoms by probing mood, feelings of guilt, suicidal ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. As recommended by the Depression Rating Scale Standardization Team, Clinical Interviewers will follow the Structured Interview Guide and use GRID scoring, in which dimensions of intensity and frequency of a symptom are rated independently for each item. Higher scores reflect greater symptom severity, categorized as Normal (0-7), Mild Depression (8-13), Moderate Depression (14-18), Severe Depression (19-22), and Very Severe Depression (>23).
  measure: Change in self-reported depression symptoms measured by Patient Health Questionnaire-9 (PHQ-9)
  time frame: Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
  description: The Patient Health Questionnaire-9 (PHQ-9) is a 9-question self-report instrument used to assess presence and severity of depressive symptoms, with scores categorized 0-4, 5-9, 10-14, 15-19, and 20-27 as minimal, mild, moderate, moderately severe, and severe depression, respectively.
  measure: Change in MDD diagnosis measured by Structured Clinical Interview for DSM-5 Disorders (SCID)
  time frame: Intake, final, 12-week follow up, 1-year follow up
  description: The SCID is a clinician-administered semi-structured interview guide for making diagnoses according to the diagnostic criteria published in the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5). It provides diagnoses for depressive and bipolar disorders, schizophrenia spectrum and other psychotic disorders, substance use disorders, anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder),obsessive-compulsive disorder, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and adjustment disorder.
  measure: Change in suicidal thoughts measured by the Columbia-Suicide Severity Rating Scale (CSSRS)
  time frame: Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
  description: The C-SSRS will be used to assess and monitor suicide ideation and behavior. The severity of the ideation subscale is rated on a 5-point ordinal scale: 1 = wish to be dead, 2 = nonspecific active suicidal thoughts, 3 = suicidal thoughts with methods, 4 =suicidal intent, and 5 = suicidal intent with plan. Suicide behaviors are rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal,self-injurious behavior.
  measure: Average anhedonia measured by Dimensional Anhedonia Rating Scale (DARS)
  time frame: Weeks 1-8 CBT+ visits (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]), final, 12-week follow up, 1-year follow up
  description: The DARS is a self-report measure that assesses state anhedonia across multiple domains. DARS is a 17-item survey on state anhedonia divided into four domains: hobbies, food/drink, social activities, and sensory experiences. Subjects must list two activities within each of these categories that they consider their favorite and then respond to questions regarding their interest in/enjoyment of those activities on a 5-point Likert scale from "Not at all" to "Very much." During pre/post-administration, participants will be asked to respond to how they are feeling "right now."
  measure: Average anhedonia measured by an Anhedonia Visual Analogue Scale (Anhedonia VAS)
  time frame: Weeks 1-8 CBT+ visits (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]), final, 12-week follow up, 1-year follow up
  description: An anhedonia Visual Analog Scale [VAS] with 0 indicating 'No pleasure at all' and 100 indicating 'Greatest pleasure imaginable' will be used to measure anhedonia. In past research by the PI, correlations between the DARS and VAS were 0.49-0.69 indicating a moderate-to-strong agreement between the measures. The VAS will be used to provide a supplementary assessment of anhedonia.
  measure: Serum brain derived neurotrophic factor (BDNF)
  time frame: Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)
  description: Serum BDNF will be quantified from a standard blood draw. Blood samples collected during Visits 1, 4, and 8 will be allowed to clot for 30 minutes and then centrifuged for ten minutes at 5500 RPM and 4 ◦C. Following centrifugation, blood serum will be extracted with samples stored at -80 ◦C until BDNF analysis. Enzyme-linked immunosorbent assay (ELISA) kits will measure the concentration of total BDNF in the serum according to the manufacturer's instructions. Each blood sample will be run in duplicate and averaged.
  measure: Change in monitor-assessed physical activity measured by accelerometry
  time frame: Intake, weeks 4 & 8 CBT+ visits (monitors worn 1 week following each time point)
  description: Participants will place an activPAL on the midline of the thigh on either leg and wear the monitor during all waking hours, removing it only for water-based activities (e.g., swimming). For data to be valid, the monitor must have been worn for 20 hours on at least 4 days, including a minimum of 3 weekdays and 1 weekend day. Sleep time will be parsed out from each day's sitting/lying time automatically using PALanalysis. From these data, average minutes of sitting per day will be used to assess total sedentary time, minutes of stepping time with a cadence ≥75 and <100 will be used to assess minutes of light-intensity physical activity and minutes of stepping time with a cadence ≥100 will be used to assess minutes of moderate to vigorous physical activity (MVPA).
  measure: Change in self-reported physical activity measured by the International Physical Activity Questionnaire - Short Form (IPAQ-SF)
  time frame: Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up
  description: The IPAQ is a physical activity questionnaire that inquires about average amounts of walking, moderate physical activity, vigorous physical activity, and sitting time per week.
  measure: Change in quality of life measured by the 36-Item Short Form Health Survey (SF-36)
  time frame: Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up
  description: The SF-36 assesses health-related quality of life. It consists of eight scaled scores (including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher the score the less disability (i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability).
  measure: Change in anxiety measured by Generalized Anxiety Disorder 7 (GAD-7)
  time frame: Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up
  description: Generalized Anxiety Disorder 7 (GAD-7) is a self-reported questionnaire for measuring generalized anxiety disorder. GAD-7 has seven items, which measure the severity of various signs of GAD according to reported response categories of: Not at all (0 points), Several days (1 point), More than half the days (2 points), and Nearly every day (3 points), with scores of 5, 10, and 15 as cut-off points for mild, moderate and severe anxiety, respectively.
  measure: Average automatic thoughts measured by Automatic Thoughts Questionnaire (ATQ)
  time frame: Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
  description: The ATQ is a 30-item instrument that measures the frequency of automatic negative statements about the self. Each item is rated on the frequency of an occurrence from "not at all" to "all the time". Total scores are the sum of all 30 items, with higher totals indicating a higher level of automatic negative self-statements.
  measure: Average session effectiveness measured by Session Evaluation Questionnaire (SEQ)
  time frame: Weeks 1-8 CBT+ visits
  description: Session Evaluation Questionnaire (SEQ) will be used to evaluate session effectiveness. This includes responses to twenty-one items in a 7-point bipolar adjective format questionnaire to assess how the client feels about each CBT session. The questionnaire assesses session depth, smoothness, positivity, and arousal. An overall score of the average of the values across each subscale will be used in this study.
  measure: Average Lyssn generated scores
  time frame: Weeks 1-8 CBT+ visits
  description: Lyssn is an AI-powered assessment platform for recording and managing session files, and all clinical interviews and therapy sessions will be recorded on the Lyssn platform. Lyssn will process the audio files from therapy sessions to generate session-level data regarding collaboration and empathy as metrics related to the primary client ratings of working alliance, as well as generating CTRS fidelity metrics which will be used in the ongoing supervision and fidelity monitoring of all sessions.
  measure: Nature Connectedness Index (NCI)
  time frame: Intake, Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)
  description: The NCI consist of 6 questions pertaining to nature connectedness. Participants respond using a 7-point Likert scale, ranging from 1 (Strongly Disagree) to 7 (Strongly Agree), with higher scores indicating greater levels of nature connectedness.
  measure: Health History Questions
  time frame: Intake
  description: Health history will be self-reported. In addition, participants will be asked to list their current medications.
  measure: Demographic Questionnaire
  time frame: Intake
  description: Demographic characteristics including age, sex, race, education, marital status, occupational status, and household income will be recorded or measured to characterize the sample.
  measure: Adverse Childhood Experience Survey (ACES)
  time frame: Intake
  description: The ACES consists of 16 questions pertaining to the respondents' first 18 years of life. Participants respond with yes or no regarding if a childhood adverse event occurred. Adverse events questions are grouped by categories. Participants are scored for each event category they are exposed to with scores ranging from 0 (unexposed) to 7 (exposed to all categories).
  arm group label: ActiveCBT
  arm group type: Experimental
  description: Participants will complete a standardized 30-minute exercise session on a stationary bike prior to therapy. Participants will view one of 8 standardized 30-minute nature documentary videos while exercising.
  arm group label: CalmCBT
  arm group type: Active Comparator
  description: Participants will view one of 8 standardized 30-minute nature documentary videos while resting quietly prior to therapy.
  intervention type: Behavioral
  intervention name: ActiveCBT
  description: Participants will complete a standardized 30-minute aerobic exercise session on a stationary bicycle prior to therapy. Supervised exercise sessions will consist of steady-state exercise at a moderate intensity corresponding to a '13' or 'somewhat hard' rating of perceived exertion. Continuous monitoring of heart rate, resistance/load, and RPE will occur throughout exercise. To closely match the groups, participants will also view 30-minute nature videos while exercising.
  arm group label: ActiveCBT
  intervention type: Behavioral
  intervention name: CalmCBT
  description: Participants will view one of 8 standardized 30-minute nature videos while resting quietly prior to therapy. These are emotionally neutral videos and will allow for participants in both groups to have the same amount of attention and contact time.
  arm group label: CalmCBT
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Jacob Meyer, PhD
  phone: 515-294-1386
  email: jdmeyer3@iastate.edu
  responsible party type: Principal Investigator
  investigator affiliation: Iowa State University
  investigator full name: Jacob Meyer
  investigator title: Associate Professor, Kinesiology
  mesh term: Depression
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major
  provided document: 