RESISTance Exercise for Depression Trial

NCT06110897 | Recruiting DMC

• 5 other identifiers: 2025-02951R01MH130566-01A1Protocol Version 9/15/2025A176000EDUC/KINESIOLOGY
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

Depression is a leading cause of disability worldwide and current treatments are ineffective for many people. This trial will investigate the efficacy of a 16-week high vs low dose resistance exercise training program for the treatment of Major Depressive Disorder (MDD) in 200 adults.

Conditions

Major Depressive Disorder

Keywords

Resistance Exercise Training; Strength Training

Outcome Measures

Primary Outcomes (4)

• Change in depressive symptom severity 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).

  Weeks 0, 8, 16, 26, 52

• Change in self-reported depression symptom severity measured by Quick Inventory of Depressive Symptoms (QIDS)

  This is a self-administered 16-item questionnaire that assesses the severity of nine depressive symptoms in the last 7 days. Each item is rated on a 4-point scale (0-3), with total scores ranging from 0-27. Higher scores indicate more severe depression. This assessment is recommended because it is free, easily administered as a self-reported instrument for adults, and captures general symptoms of depression.

  Weeks 0, 1-16 (once per week across the intervention), 26, 52

• Cerebral mean blood velocity

  Cerebral blood velocity will be measured under supine, resting conditions using non-invasive techniques following 10 min of quiet rest in a dimly lit room. Measurements will be taken from the middle (MCA, primary outcome) and anterior cerebral artery (ACA, secondary outcome) following standardized, recommended insonation protocols using 2 megahertz (MHz) transcranial Doppler (TCD) probes secured to the temporal window via a headset. MCA blood velocity waveforms will be collected over a 90-sec epoch and averaged. MCA mean blood velocity will be calculated using a standard algorithm implemented on the device.

  Weeks 0, 8, 16, 26, 52

• Cerebral blood velocity pulsatility

  Cerebral blood pulsatility will be measured using the same techniques and conditions described for cerebral mean blood velocity, above for the MCA (primary outcome) and ACA (secondary outcome). Cerebral pulsatility will be quantified using the pulsatility index, calculated as (systolic - diastolic velocity)/mean velocity.

  Weeks 0, 8, 16, 26, 52

Secondary Outcomes (25)

• Changes in general self efficacy measured by New General Self-Efficacy Scale

  Weeks 0, 8, 16, 26, 52

• Changes in RET-specific self efficacy measured by a modified version of the New General Self-Efficacy Scale

  Weeks 0, 1-16 (once per week across the intervention), 26, 52

• Change in suicidal thoughts measured by Columbia-Suicide Severity Rating Scale (CSSRS)

  Weeks 0, 8, 16, 26, 52

• Change in muscular strength measured by Estimated 1 Repetition Maximum (RM) Strength Test

  Weeks 0, 8, 16, 26, 52

• Change in grip strength

  Weeks 0, 8, 16, 26, 52

Other Outcomes (1)

• Major depressive disorder diagnosis assessed using Structured Clinical Interview for DSM-5 Disorders (SCID)

  Weeks 0, 8, 16, 26, 52

Study Arms (2)

High Dose Resistance Exercise Training

EXPERIMENTAL

Participants will complete a 16-week, twice/week progressive program beginning at a moderate intensity. Each session will last \~60 minutes and begin and end with a 5-minute warm-up/cool-down. Training will begin with standard familiarization sessions to introduce participants to the machines, teach correct lifting techniques, and ensure participant safety and comfort with each exercise machine. Participants will perform 3 sets of 8-12 repetitions on 9 different machines (i.e., leg press, hamstring curl, quadriceps extension, chest press, lat pulldown, shoulder press, biceps curl, triceps extension) and one body weight/free-weight abdominal exercise. Workload will begin at 60% of estimated 1-RM and will systematically and progressively increase during the intervention.

Behavioral: High Dose Resistance Exercise Training

Low Dose Resistance Exercise Training

ACTIVE COMPARATOR

Participants will complete a 16-week, twice/week progressive program beginning at a low intensity. Each session will last \~60 minutes and begin and end with a 5-minute warm-up/cool-down. Training will begin with standard familiarization sessions to introduce participants to the machines, teach correct lifting techniques, and ensure participant safety and comfort with each exercise machine. Participants will perform 3 sets of 8-12 repetitions on 9 different machines (i.e., leg press, hamstring curl, quadriceps extension, chest press, lat pulldown, shoulder press, biceps curl, triceps extension) and one body weight/free-weight abdominal exercise. Workload will begin at 30% of estimated 1-RM and will systematically and progressively increase during the intervention.

Behavioral: Low Dose Resistance Exercise Training Group

Interventions

High Dose Resistance Exercise Training BEHAVIORAL

Progressive resistance exercise training

High Dose Resistance Exercise Training

Low Dose Resistance Exercise Training Group BEHAVIORAL

Progressive resistance exercise training

Low Dose Resistance Exercise Training

Eligibility Criteria

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

You may qualify if:

• Be diagnosed with DSM-5 MDD, confirmed via Structured Clinical Interview for DSM-5 (SCID).
• Have current depressive symptoms of at least mild severity defined by the Hamilton Rating Scale of Depression 17 greater than or equal to 8 (HAMD; using the GRID-HAMD evaluated by trained, masked raters)
• Be ages 18-65
• EITHER not taking any mental health medications or seeking 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 intend to maintain that regimen for the duration of the study
• Safe to exercise based on physical activity screening questions or physician clearance
• Willing to be randomized to either condition
• have a Smartphone

You may not qualify if:

• Currently pregnant, nursing, or planning to become pregnant during the trial
• Class III+ obesity
• Diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID
• Diagnosed with current Substance Use Disorder, via the SCID
• Active suicidal ideation with specific plan and intent ('5' score on Suicidal Ideation from Columbia Suicide Severity Rating Scale), which would necessitate immediate emergent care
• Exhibit behavioral disturbance (e.g., aggression, mild-moderate cognitive impairment) that would significantly interfere with study participation, as assessed by clinical research personnel
• Currently meets resistance exercise recommendations (2 days per week) for the last 8 weeks
• Self-reporting a concussion/traumatic brain injury within the last 3 months
• Having cardiovascular disease, uncontrolled hypertension, or uncontrolled diabetes

Sponsors & Collaborators

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

Study Sites (2)

Iowa State University

Ames, Iowa, 50010, United States

COMPLETED

University of Wisconsin - Madison

Madison, Wisconsin, 53705, United States

RECRUITING

Related Publications (1)

• Meyer JD, Smith SL, Gidley JM, Molina A, Churchill SL, Kelly SJE, Lansing JE, Wade NG, Phillips AL, Liu P, Herring MP, Murray TA, Barnes JN, Goldberg SB, Lefferts WK. Protocol for a randomized controlled trial of a resistance exercise training to treat major depression via cerebrovascular mechanisms (RESIST Trial). Trials. 2025 Aug 26;26(1):306. doi: 10.1186/s13063-025-09025-z.

  PMID: 40859378 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Jacob Meyer, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Taline Jouzi

CONTACT

608-890-0154; jouzi@wisc.edu

Jeni Lansing

CONTACT

jlansing3@wisc.edu

Study Design

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

Study Record Dates

• First Submitted: October 20, 2023
• First Posted: November 1, 2023
• Study Start: January 1, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): October 31, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-04

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 (2)