Exercise-priming of CBT for Depression: the CBT+ Trial

NCT07221929 | Recruiting DMC

• 4 other identifiers: 2025-1128R33MH129407EDUC/KINESIOLOGYProtocol Version 12/19/25
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the effects of intentionally sequencing aerobic exercise immediately prior to cognitive behavioral therapy (CBT) to determine its effects on mechanisms of CBT (i.e., working alliance, behavioral activation). To assess the utility of this treatment augmentation, investigators will conduct a randomized controlled trial involving 100 adults with Major Depressive Disorder who will watch a nature documentary while either resting quietly ( 'CalmCBT') or exercising at a moderate intensity ('ActiveCBT') immediately prior to 8 weekly sessions of CBT.

Conditions

Major Depressive Disorder

Keywords

cognitive behavioral therapy; CBT

Outcome Measures

Primary Outcomes (4)

• Working Alliance Inventory (WAI) - Bond subscale

  The WAI-Bond subscale scores 4 items, with scores ranging from 4-28. Higher scores are stronger perceived patient-therapist bond: how the participant experiences feelings of bond (i.e., feelings of mutual trust, acceptance, and connection) with their therapist.. The Bond subscale is a primary outcome measure for this study and the total score will be analyzed as a secondary outcome.

  data collected at each CBT session (weeks 1-8)

• Behavioral Activation for Depression Scale (BADS)

  BADS is a 25-item survey, each item scored from 0 (not at all) to 6 (completely), with some items reverse scored. There are 4 sub-scales: Activation, Avoidance / Rumination, Work / School Impairment, Social Impairment. The total possible range of scores is from 0 to 150 where higher scores indicate higher behavioral activation (increased avoidance and impairment).

  data collected at baseline, each CBT session (weeks 1-8), post intervention visit (week 9), week 20, week 52

• GRID Hamilton Rating Scale for Depression (GRID-HAMD)

  The GRID-HAM-D is a 17-item 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 (greater than 23).

  baseline, post intervention visit (week 9), week 20, week 52

• Patient Health Questionnaire-9 (PHQ-9)

  The PHQ-9 is a 9-item questionnaire that asks the participant to consider the last 2 weeks and score each question from 0-3 for a total possible range of scores from 0-27 where higher scores indicate increase depression.

  data collected at baseline, each CBT session (weeks 1-8), post intervention visit (week 9), week 20, week 52

Secondary Outcomes (19)

• Structured Clinical Interviews for DSM-5 Disorders (SCID)

  baseline, post intervention visit (week 9), week 20, week 52

• Columbia Severity Suicide Rating (CSSRS)

  data collected at baseline, each CBT session (weeks 1-8), post intervention visit (week 9), week 20, week 52

• Dimensional Anhedonia Rating Scale (DARS)

  Weeks 1-8 CBT sessions (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]), final visit (week 9), 20-week follow up, 1-year follow up

• Visual Analogue Scale (VAS)

  Weeks 1-8 CBT sessions (repeated 3 times [before exercise/calm condition, immediately after exercise/calm condition, and after therapy]), final visit (week 9), 20-week follow up, 1-year follow up

• Serum Brain Derived Neurotrophic Factor (BDNF)

  Weeks 1, 4, and 8 CBT sessions (before exercise/calm condition, immediately after exercise/calm condition, and after therapy)

Other Outcomes (4)

• Health history questions

  Baseline, any changes reported at week 9 for medication and service use

• Demographic questionnaire

  Baseline

• Adverse Childhood Experience Survey (ACES)

  Baseline

Study Arms (2)

CalmCBT

EXPERIMENTAL

In this arm, participants would complete 30 minutes of rest while watching a nature documentary before cognitive behavioral therapy

Behavioral: Rest

ActiveCBT

EXPERIMENTAL

In this arm, participants would complete 30 minutes of aerobic activity before cognitive behavioral therapy, while watching the same nature documentary the CalmCBT group watches.

Behavioral: Aerobic Activity

Interventions

Rest BEHAVIORAL

30 minutes of rest while watching a nature documentary before cognitive behavioral therapy

CalmCBT

Aerobic Activity BEHAVIORAL

30 minutes of aerobic activity before cognitive behavioral therapy, while watching the same nature documentary the CalmCBT group watches.

ActiveCBT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a diagnosis of DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-5) MDD, confirmed via Structured Clinical Interview for DSM-5 (SCID)
• current depressive symptoms of at least mild severity defined by a Hamilton Rating Scale of Depression (using the GRID-HAMD) score greater than or equal to 8
• EITHER not currently take any mental health medications or use other mental health treatment (e.g., behavioral, psychological) OR be on a stable mental health medication and/or treatment regimen for the past 8 weeks, and encouraged to maintain that regimen for the duration of the 8 week intervention period
• willing and safe to perform exercise based on responses on the Physical Activity Readiness Questionnaire (rules out contraindications to exercise)
• reported being CBT-naïve (as defined by never undergoing structured CBT).

You may not qualify if:

• reporting being currently pregnant, nursing, or planning to become pregnant during the study
• being diagnosed with current Substance Use Disorder, via the SCID
• being diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID
• having class III+ obesity (BMI greater than or equal to 40)
• active suicidal ideation with specific plan and intent ('5' score on Suicidal Ideation from Columbia Suicide Severity Rating Scale \[C-SSRS\])
• exhibiting behavioral disturbance (e.g., aggression, mild-moderate cognitive impairment) or relationships with the study team members (e.g., therapists) that would significantly interfere with study participation, as assessed by research personnel.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Related Publications (1)

• Meyer JD, Kelly SJE, Gidley JM, Lansing JE, Smith SL, Churchill SL, Thomas EBK, Goldberg SB, Abercrombie HC, Murray TA, Wade NG. Protocol for a randomized controlled trial: exercise-priming of CBT for depression (the CBT+ trial). Trials. 2024 Oct 7;25(1):663. doi: 10.1186/s13063-024-08495-x.

  PMID: 39375728 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

RE1-silencing transcription factor; Exercise

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Jacob Meyer, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madeleine Connolly, PhD

CONTACT

(608) 890-0154; mconnolly5@wisc.edu

Jeni Lansing, PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2025
• First Posted: October 28, 2025
• Study Start: January 5, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: IPD will be available one year after the final NIMH NDA data upload.
• Access Criteria: Individuals who submit request to access for IPD to NIMH NDA may be able to access the data.

Locations

US (1)