RESISTance Exercise for Depression Trial

University of Wisconsin (UW)

Status: Enrolling

Conditions: Major Depressive Disorder

Treatments: Behavioral: Low Dose Resistance Exercise Training Group; Behavioral: High Dose Resistance Exercise Training

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06110897

2025-0295

A176000 (Other Identifier)

1R01MH130566-01A1 (U.S. NIH Grant/Contract)

Protocol Version 9/15/2025 (Other Identifier)

EDUC/KINESIOLOGY (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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200 participants in 2 patient groups

High Dose Resistance Exercise Training

Experimental group

Description:

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.

Treatment:

Behavioral: High Dose Resistance Exercise Training

Low Dose Resistance Exercise Training

Active Comparator group

Description:

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.

Treatment:

Behavioral: Low Dose Resistance Exercise Training Group