RESISTance Exercise for Depression Trial

NCT ID: NCT06110897

Last Updated: 2025-10-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-01
• Study Completion Date: 2028-05-31

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.

Detailed Description

Frontline treatments for major depressive disorder (MDD), including psycho- and pharmacotherapy, have limited effectiveness, and there is a critical need to develop and test novel, efficacious treatments for MDD and simultaneously work to optimize its benefits. Resistance exercise training (RET) is a promising but understudied treatment approach. This trial will investigate the efficacy of RET for treatment of MDD in a 1:1 randomized controlled trial (n=200) of 16 weeks of high vs low progressive RET in adults with DSM-5 diagnosed MDD. Further, this project will explore potential mechanisms leading to symptom improvement, including changes in cerebrovascular function (i.e., cerebral blood velocity and pulsatility) and self-efficacy, while also using supervised machine learning tools to predict depression changes, cerebrovascular changes, and participant adherence. Upon completion, this study will build towards identifying and translating mechanistically driven behavioral treatments to reduce the global burden of mental illness.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

High Dose Resistance Exercise Training

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.

Group Type: EXPERIMENTAL

High Dose Resistance Exercise Training

Intervention Type: BEHAVIORAL

Progressive resistance exercise training

Low Dose Resistance Exercise Training

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.

Group Type: ACTIVE_COMPARATOR

Low Dose Resistance Exercise Training Group

Intervention Type: BEHAVIORAL

Progressive resistance exercise training

Interventions

High Dose Resistance Exercise Training

Progressive resistance exercise training

Intervention Type: BEHAVIORAL

Low Dose Resistance Exercise Training Group

Progressive resistance exercise training

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Iowa State University

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

University of Limerick

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacob Meyer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

Iowa State University

Ames, Iowa, United States

Site Status: COMPLETED

University of Wisconsin - Madison

Madison, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Taline Jouzi

Role: CONTACT

jouzi@wisc.edu

608-890-0154

Jeni Lansing

Role: CONTACT

jlansing3@wisc.edu

Facility Contacts

Taline Jouzi

Role: primary

jouzi@wisc.edu

608-890-0154

References

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.

Reference Type: DERIVED

PMID: 40859378 (View on PubMed)

Other Identifiers

1R01MH130566-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Protocol Version 9/15/2025

Identifier Type: OTHER

Identifier Source: secondary_id

A176000

Identifier Type: OTHER

Identifier Source: secondary_id

EDUC/KINESIOLOGY

Identifier Type: OTHER

Identifier Source: secondary_id

2025-0295

Identifier Type: -

Identifier Source: org_study_id