CBT+ for Depression

Major Depressive Disorder Clinical Trial

— CBT+  

Official title:

ActiveCBT for Depression: Transforming Treatment Through Exercise Priming

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06001346
• Other study ID #: 1R61MH129407
• Secondary ID: 1R61MH129407-01A
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: September 2023
• Source: Iowa State University
• Contact: Jacob Meyer, PhD
• Phone: 515-294-1386
• Email: jdmeyer3[@]iastate.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosed with DSM-5 MDD, confirmed via SCID.

• Having current depressive symptoms of at least mild severity defined by HAM-D rating =8.

• Being between age 18 and 65.

• Either not engaging in any mental health treatment (e.g., medication, psychological, or behavioral) OR on a stable mental health treatment regimen and willing to maintain it for the length of the intervention.

• Willing and safe to exercise based on the Physical Activity Readiness Questionnaire.

• Being CBT-naïve (as defined by never undergoing structured CBT).

Exclusion Criteria:

• currently pregnant, nursing, or planning to become pregnant,

• severe obesity (BMI=40)

• diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID

• diagnosed with current Substance Use Disorder, via the SCID

• pose an imminent risk of self-harm or harm to others, assessed via the C-SSRS

• exhibit behavioral disturbance (e.g., aggression, mild-moderate cognitive impairment) that would significantly interfere with study participation, assessed by clinical research personnel

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Behavioral:
• ActiveCBT
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.
• CalmCBT
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.

Locations

Country	Name	City	State
United States	Iowa State University	Ames	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Iowa State University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health History Questions	Health history will be self-reported. In addition, participants will be asked to list their current medications.	Intake
Other	Demographic Questionnaire	Demographic characteristics including age, sex, race, education, marital status, occupational status, and household income will be recorded or measured to characterize the sample.	Intake
Other	Adverse Childhood Experience Survey (ACES)	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).	Intake
Primary	Average self-reported working alliance measured by Working Alliance Inventory (WAI)	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.	Weeks 1-8 CBT+ visits
Primary	Average change in self-reported behavioral activation measured by Behavioral Activation for Depression Scale (BADS)	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.	Intake, Weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
Secondary	Changes in clinician-rated depression symptoms measured by GRID-Hamilton Depression Rating Scale (GRID-HAM-D)	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).	Intake, final, 12-week follow up, 1-year follow up
Secondary	Change in self-reported depression symptoms measured by Patient Health Questionnaire-9 (PHQ-9)	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.	Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
Secondary	Change in MDD diagnosis measured by Structured Clinical Interview for DSM-5 Disorders (SCID)	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.	Intake, final, 12-week follow up, 1-year follow up
Secondary	Change in suicidal thoughts measured by the Columbia-Suicide Severity Rating Scale (CSSRS)	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.	Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
Secondary	Average anhedonia measured by Dimensional Anhedonia Rating Scale (DARS)	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."	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
Secondary	Average anhedonia measured by an Anhedonia Visual Analogue Scale (Anhedonia VAS)	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.	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
Secondary	Serum brain derived neurotrophic factor (BDNF)	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.	Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)
Secondary	Change in monitor-assessed physical activity measured by accelerometry	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).	Intake, weeks 4 & 8 CBT+ visits (monitors worn 1 week following each time point)
Secondary	Change in self-reported physical activity measured by the International Physical Activity Questionnaire - Short Form (IPAQ-SF)	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.	Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up
Secondary	Change in quality of life measured by the 36-Item Short Form Health Survey (SF-36)	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).	Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up
Secondary	Change in anxiety measured by Generalized Anxiety Disorder 7 (GAD-7)	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.	Intake, week 4 CBT+ visit, final, 12-week follow up, 1-year follow up
Secondary	Average automatic thoughts measured by Automatic Thoughts Questionnaire (ATQ)	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.	Intake, weeks 1-8 CBT+ visits, final, 12-week follow up, 1-year follow-up
Secondary	Average session effectiveness measured by Session Evaluation Questionnaire (SEQ)	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.	Weeks 1-8 CBT+ visits
Secondary	Average Lyssn generated scores	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.	Weeks 1-8 CBT+ visits
Secondary	Nature Connectedness Index (NCI)	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.	Intake, Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)