Major Depressive Disorder
Conditions
Keywords
Exercise Priming, Depression, Cognitive Behavioral Therapy
Brief 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.
Detailed 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.
Interventions
BEHAVIORALActiveCBT
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.
BEHAVIORALCalmCBT
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.
Sponsors
University of Wisconsin, Madison
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Self-reported Working Alliance Measured by Working Alliance Inventory (WAI) | Weeks 1-8 CBT+ visits | 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 total range of scores is from 12-84 with higher scores indicating a better therapeutic alliance. |
| Self-reported Behavioral Activation Measured by Behavioral Activation for Depression Scale (BADS) | Intake, Weeks 1-8 CBT+ visits, Week 9 (Post-therapy), 12-week follow up, 1-year follow-up | 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. Each item is rated on a 7-point scale from 0 (Not at all) to 6 (Completely) with total scores ranging: 0-150 where higher scores indicate greater behavioral activation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician-rated Depression Symptoms Measured by GRID-Hamilton Depression Rating Scale (GRID-HAM-D) From Intake | Intake, Week 9 (Post-therapy), 12-week follow up, 1-year follow up | 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. Total scores are calculated from each question and range from 0 to 52, with higher scores indicated greater depressive symptom severity. |
| Change in Self-reported Depression Symptoms Measured by Patient Health Questionnaire-9 (PHQ-9) From Week 1 | Weeks 1-8 CBT+ visits, Week 9 (Post-therapy), 12-week follow up, 1-year follow-up | 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. |
| MDD Diagnosis Measured by Structured Clinical Interview for DSM-5 Disorders (SCID) | Intake, Week 9 (Post-therapy), 12-week follow up, 1-year follow up | 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 inclusion and exclusionary diagnoses. Results show number of participants who meet criteria for Major Depressive Disorder (i.e., 'checked') or no longer meet criteria (i.e., 'unchecked'). |
| Average Anhedonia Measured by Dimensional Anhedonia Rating Scale (DARS) | Weeks 1-8 CBT+ visits (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]) | 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" (0) to "Very much" (4), with total scores ranging from 0 to 68, with higher scores representing reduced anhedonia. |
| Average Anhedonia Measured by an Anhedonia Visual Analogue Scale (Anhedonia VAS) | Weeks 1-8 CBT+ visits (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]) | 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. The VAS will be used to provide a supplementary assessment of anhedonia. |
| Serum Brain Derived Neurotrophic Factor (BDNF) | Weeks 1, 4, and 8 CBT+ visits (before exercise/calm condition, immediately after exercise/calm condition, and after therapy) | 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. |
| Change in Anxiety Measured by Generalized Anxiety Disorder 7 (GAD-7) From Intake | Intake, week 4 CBT+ visit, Week 9 (Post-therapy), 12-week follow up, 1-year follow up | 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). A total score is calculated ranging from 0 to 21, with higher scores indicating more severe anxiety symptoms. |
| Average Automatic Thoughts Measured by Automatic Thoughts Questionnaire (ATQ) | Intake, weeks 1-8 CBT+ visits, Week 9 (Post-therapy), 12-week follow up, 1-year follow-up | 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 (ranging 30-150), with higher totals indicating a higher level of automatic negative self-statements. |
| Average Session Effectiveness Measured by Session Evaluation Questionnaire (SEQ) | Weeks 1-8 CBT+ visits | 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 subscales will be used in this study (ranging 7-28). Higher scores indicate more favorable session evaluations. |
Countries
United States
Participant flow
Pre-assignment details
379 potential participants were screened online (119 excluded); 260 potential participants went on to complete a phone screen (176 excluded or declined to participate), 84 of them completed an intake assessment (44 excluded), and 40 participants were randomized as an intention to treat sample.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.9 years STANDARD_DEVIATION 13.3 |
| Currently in Therapy | 8 Participants |
| Education College Graduate | 8 Participants |
| Education Graduate Degree | 6 Participants |
| Education High School Graduate | 1 Participants |
| Education Some College | 11 Participants |
| Education Some Postgraduate School | 3 Participants |
| Employment Full Time | 7 Participants |
| Employment Other | 0 Participants |
| Employment Part Time | 6 Participants |
| Employment Student | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Income $100,000 or more | 4 Participants |
| Income $25,000-$49,999 | 5 Participants |
| Income $50,000-$74,999 | 1 Participants |
| Income $75,000-$99,999 | 2 Participants |
| Income Less than $25,000 | 8 Participants |
| Marital Status Married / Partnered | 17 Participants |
| Marital Status Single / Separated / Divorced | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 19 participants |
| Sex/Gender, Customized Female | 12 Participants |
| Sex/Gender, Customized Gender nonconforming | 1 Participants |
| Sex/Gender, Customized Male | 6 Participants |
| Using Any Mental Health Medication | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 21 |
| other Total, other adverse events | 0 / 19 | 0 / 21 |
| serious Total, serious adverse events | 0 / 19 | 0 / 21 |
Outcome results
None listed