Exercise Training for Managing Major Depressive Disorder in Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this research is to examine the effects of two different exercise training regimens for managing depression and improving other health indicators among persons with multiple sclerosis (MS). The project will enroll persons with MS and major depressive disorder (MDD) between 18 and 64 years of age. The investigators will enroll a total of 146 participants. This is a Phase-II trial that compares the efficacy of an exercise training program (POWER-MS) compared with a stretching program (FLEX-MS) for immediate and sustained reductions in the severity of depression among persons with MS who have MDD.

Official Title
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Exercise Training for Managing Major Depressive Disorder in Multiple Sclerosis

Conditions
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Multiple Sclerosis, Major Depressive Disorder

Intervention / Treatment
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* Behavioral: POWER-MS
* Behavioral: FLEX-MS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Physical confirmed diagnosis of Multiple Sclerosis (MS) Diagnosis of Major Depressive Disorder (MDD) - see below (MINI) English as primary language Eligible age (between 18 and 64 years old) Relapse and steroid free in past 30 days Internet and email access Willingness to complete the testing and questionnaires, wear the accelerometer, undergo randomization, and engage in exercise testing Exclusion Criteria Godin Leisure Time Exercise Questionnaire (GLTEQ): Exclude if health contribution score of 14 units or more. This assessment is administered to confirm insufficient baseline physical activity (i.e., not meeting current PA guidelines) Patient Determined Disease Steps (PDDS): Exclude if score above '2' (i.e., greater than mild ambulatory disability). This assessment is administered as the proposed intervention focuses on walking as main modality for exercise training. The scale asks the participant to describe their walking situation on a scale of 0 to 8; where lower scores indicate better walking ability. Beck Depression Inventory-Fast Screen (BDI-FS): Exclude if a score less than '4'. The scale measures depression and those with a score of '4' or below likely have very mild depression resulting in floor effects and/or spontaneous remission. Physical Activity Readiness Questionnaire (PAR-Q): Exclude if more than one yes/affirmative response on this 7-item self-report assessment. This assessment is administered to exclude those individuals who are at a moderate to high risk for contraindications of injury or possible death when undertaking strenuous or maximal exercise. This is a 7-item self-report tool where more than one yes/affirmative response indicates that an individual is not recommended to engage in physical activity within the capacity of this study. Those scoring more than one yes/affirmative response will be further advised to seek medical guidance before becoming more physically active. Telephone Interview for Cognitive Status (TICS-M): Exclude if scores less than 18. This assessment is administered to ensure that all participants can adequately follow directions. The application of the TICS-M is to ensure that participants do not have severe cognitive impairment that might preclude the ability to adhere to the conditions, understand intervention content, and interact with behavior coaches. MINI International Neuropsychiatric Interview (version 7.0.2) based on the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V): Include those who meet the criteria for MDD, but exclude for other severe mental illness (obsessive-compulsive disorder, schizophrenia, bipolar or other psychotic disorders) as indicated by the MINI; these persons would require more intensive mental health treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POWER-MS<br>The POWER-MS condition will deliver the Guidelines for Exercise in MS (GEMS) program with a remotely coached/guided, home-based setting using telerehabilitation. GEMS recommends 30 minutes of moderate intensity aerobic activity, 3x/week AND strength training exercises for major muscle groups, 3x/week. | Behavioral: POWER-MS<br>* The POWER-MS intervention includes both aerobic exercise and resistance exercise: Aerobic Exercise: The goal of the aerobic exercise training is for participants to achieve three moderate-intensity walking sessions of 30+ minutes per session by the end of the 16-week intervention. Resistance Exercise: Participants will complete resistance exercise training that consists of 1-2 sets (10-15 repetitions) of 5-10 exercises targeting the lower body, upper body, and core muscle groups performed three days per week, with the sets, repetitions and number of exercises increasing based on an individualized difficulty level.<br>|
| Active Comparator: FLEX-MS<br>The FLEX-MS condition will primarily focus on flexibility as the applicable exercise modality. As such, the program will emphasize that flexibility is an important component of fitness. The goal would be for each participant to enhance their flexibility by engaging in a titrated exercise prescription where the number of sets and time to hold per set will increase throughout the 16-week program. | Behavioral: FLEX-MS<br>* The FLEX-MS intervention is specifically a stretching exercise prescription. All exercise movements are consistent throughout the program. At the beginning of the program, the stretching exercise sessions will take five minutes (1 set) three days per week (15 minutes per week). By the end of the 16-week program, the sessions will take about 30 minutes (2 sets) to be performed three days per week (1.5 hours per week).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression Severity (self-report) | Patient Health Questionnaire (PHQ-9); scores range between 0 (min) and 27 (max), higher scores indicate greater depression severity. | baseline (week 0), immediate follow-up (week 16 or 4 months), and long-term follow-up (week 32 or 8 months) | 
| Change in Depression Severity (observer-rated) | Hamilton Depression Rating Scale (HDRS-17); scores range between 0 (min) and 21 (max), higher scores reflect greater frequency of depressive symptoms. | baseline (week 0), immediate follow-up (week 16 or 4 months), and long-term follow-up (week 32 or 8 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Perception of Fatigue Severity | Fatigue Severity Scale (FSS); scores range between 1 (min) and 7 (max), higher scores reflect greater fatigue severity. | baseline (week 0), immediate follow-up (week 16 or 4 months), and long-term follow-up (week 32 or 8 months) | 
| Change in Cognitive Performance | Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). The BICAMS includes Symbol Digit Modalities Test (SDMT), first five learning trials of the California Verbal Learning Test-II (CVLT-II), and first three learning trials of the Brief Visuospatial Memory Test-Revised (BVMT-R). SDMT scores range between 0 (min) and 110 (max), higher scores indicate better performance. CVLT-II scores range between 0 (min) and 80 (max), higher scores indicate better performance. BVMT-R scores range between 0 (min) and 36 (max), higher scores indicate better performance. | baseline (week 0), immediate follow-up (week 16 or 4 months), and long-term follow-up (week 32 or 8 months) | 
| Change in Quality of Life | Multiple Sclerosis Impact Scale (MSIS-29); scores range between 0 (min) and 100 (max), higher scores indicate worse quality of life. | baseline (week 0), immediate follow-up (week 16 or 4 months), and long-term follow-up (week 32 or 8 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, Multiple Sclerosis, Depression, MDD, Exercise, Physical Activity, Intervention, Behavior