TRPMS to Improve Mobility and Depression in Multiple Sclerosis

Not Applicable

Withdrawn

• Conditions: Multiple Sclerosis
• Interventions: Device: TRPMS (Transcranial Rotating Permanent Magnet Stimulation); Other: Aerobic Exercise Program; Other: Computerized CT (Cognitive Training)

• Registration Number: NCT04578041
• Lead Sponsor: NYU Langone Health

Brief Summary

This study is aimed to test the efficacy of 10 sessions of Transcranial Rotating Permanent Magnetic Stimulation (TRPMS) paired with aerobic exercise or computerized cognitive training (CT) on mobility and depression symptoms in 40 individuals affected by multiple sclerosis (MS).

Participants in Arm 1 will complete 10x40 minutes daily sessions of TRPMS+aerobic exercise. Participants in Arm 2 will complete TRPMS+computerized CT. Primary outcomes for both arms will be assessed at baseline, at treatment end and after 4-week from the treatment end (follow-up).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-01
• Study First Submitted QC: 2020-10-01
• Study First Posted: 2020-10-08
• Study Start: 2023-01-01
• Primary Completion: 2023-03-05
• Study Completion: 2023-03-05
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-22
• Last Update Posted: 2023-12-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

In order to be eligible to participate in Arm 1 of this study, an individual must meet all of the following criteria:

1. Between ages 18 - 70
2. SDMT z-score ≥ -3.0
3. Wide Range Achievement Test-4th Edition (WRAT-4) Reading Recognition scaled score ≥ 85
4. Definite MS diagnosis as assessed by a licensed physician (all subtypes - RRMS, PPMS, SPMS)
5. Expanded Disability Status Scale (EDSS) ≤ 6.5
6. Clinically stable disease course with absence of relapse within the past 30 days
7. Able to understand the informed consent process and provide consent to participate in the study
8. Complete the TMS screening questionnaire
9. Able to commit to study timeframe
10. Clinically significant gate deviations (T25-FW > 5.0 seconds)
11. Able to walk independently with or without assistive device (i.e. cane, crutches, or walking frames) for medium distance
12. Able to exercise with seated elliptical machine

In order to be eligible to participate in Arm 2 of this study, an individual must meet all of the following criteria:

1. Between ages 18 - 70
2. SDMT z-score ≥ -3.0
3. Wide Range Achievement Test-4th Edition (WRAT-4) Reading Recognition scaled score ≥ 85
4. Definite MS diagnosis as assessed by a licensed physician (all subtypes - RRMS, PPMS, SPMS)
5. Expanded Disability Status Scale (EDSS) ≤ 6.5
6. Clinically stable disease course with absence of relapse within the past 30 days
7. Able to understand the informed consent process and provide consent to participate in the study
8. Complete the TMS screening questionnaire
9. Able to commit to study timeframe
10. Elevated symptoms of depression as determined by BDI of ≥ 4

Exclusion Criteria

1. Visual, auditory or motor deficits that would influence participant safety as assessed by a licensed physician
2. History of seizure or epileptic history as assessed by licensed physician
3. Medication which significantly lower the seizure threshold as assessed by licensed physician
4. Primary psychiatric disorder that would influence ability to participate
5. Uncontrolled headaches and migraine or recent changes in the rate or severity of head pressure, headache, or migraine in the past two weeks
6. History of stroke or head trauma (e.g., head injury, brain surgery) or medical device implanted in the head (e.g. Deep Brain Stimulator) or in the neck (e.g. Vagus Nerve Stimulator)
7. History of uncontrolled or labile hypertension
8. Other serious uncontrolled medical condition or recent medical traumas
9. Presence of metal or electronic implants in the body contraindicated for TMS
10. Alcohol or other substance use disorder
11. Pregnant or breastfeeding
12. History of clinically significant abnormalities on electrocardiogram (EKG) (Arm 1 only)
13. Presence of chronic medical illness and/or severe ataxia (Arm 1 only)
14. Functional surgery for lower limb in the past 6 months (e.g. hip or knee replacement) (Arm 1 only)
15. Lower limb Botulinum toxin injection within the past 2 months (Arm 1 only)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: TRPMS + Aerobic Physical Activity Program	TRPMS (Transcranial Rotating Permanent Magnet Stimulation)	-
Arm 1: TRPMS + Aerobic Physical Activity Program	Aerobic Exercise Program	-
Arm 2: TRPMS + Adaptive Cognitive Training	Computerized CT (Cognitive Training)	-
Arm 2: TRPMS + Adaptive Cognitive Training	TRPMS (Transcranial Rotating Permanent Magnet Stimulation)	-

Primary Outcome Measures

Name	Time	Method
Change in Gait Velocity	Baseline (Day 0), Day 10	To determine the primary efficacy of the TRPMS intervention paired with aerobic exercise, gait velocity will be assessed during the instrumented 10-meter walking test. Gait velocity will be measured using a wearable inertial sensor (G-Sensor).
Change in PROMIS Depression Score	Baseline (Day 0), Day 10	Arm 2: To determine the primary efficacy of the TRPMS intervention paired with computerized CT, changes in PROMIS Depression from baseline to treatment-end will be measured. The PROMIS Depression questionnaire consists of 8 items. Each item on the measure is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8 to 40 with higher scores indicating greater severity of depression.
Percent of Sessions Completed	Day 10	Feasibility of at-home usage of TRPMS device measured by percent of sessions completed (80%)

Secondary Outcome Measures

Name	Time	Method
Change in Distance Traveled During 2-Minute Walking Test	Baseline (Day 0), Day 10	Arm 1
Change in the Total Time for Completing the Timed Up and Go (TUG) test	Baseline (Day 0), Day 10	Arm 1: The test requires the subject to rise from a chair, walk 3.0 m at a comfortable pace to a mark placed on the floor, turn around at the 3.0 m mark, walk back to the starting point, and return to sitting in the chair.
Change in Modified Fatigue Impact Scale (MFIS) Score	Baseline (Day 0), Day 10	MFIS consists of 21 statements that describe the effects of fatigue. Each statement is scored on a scale of 0-4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always). The total MFIS score can range from 0-84; the higher the score, the stronger the feelings of fatigue.
Change in Short Form (SF)-36 Score	Baseline (Day 0), Day 10	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
Change in Center for Epidemiological Studies-Depression short form (CESD-10) Score	Baseline (Day 0), Day 10	Arm 2: CESD-10 10-item Likert scale questionnaire assessing depressive symptoms in the past week. It includes three items on depressed affect, five items on somatic symptoms, and two on positive affect. Options for each item range from "rarely or none of the time" (score of 0) to "all of the time" (score of 3). The total range of score is 0-30; higher scores indicate the presence of significant depressive symptoms.
Change in Gait Velocity	Baseline (Day 0), Week 4	Arm 1: To assess sustained improvements, gait velocity will be assessed during the instrumented 10-meter walking test. Gait velocity will be measured using a wearable inertial sensor (G-Sensor).
Change in PROMIS Depression Score	Baseline (Day 0), Week 4	Arm 2: To determine the primary efficacy of the TRPMS intervention paired with computerized CT, changes in PROMIS Depression from baseline to treatment-end will be measured. The PROMIS Depression questionnaire consists of 8 items. Each item on the measure is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8 to 40 with higher scores indicating greater severity of depression.
Change in Inventory of Depressive Symptomatology Self-Report (IDS-SR) Score	Baseline (Day 0), Day 10	Arm 2: Each of the 28 items is scored on a 1 to 3 scale (0-the absence of pathology; 3-severe pathology). The total scores range from 0 to 84. The higher the score, the more severe the pathology.
Change in Patient Health Questionnaire 9 (PHQ-9) Score	Baseline (Day 0), Day 10	Arm 2: The PHQ-9 is the depression module, which scores each of the nine DSM-IV criteria as "0" (not at all) to "3" (nearly every day). A PHQ-9 score ≥10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively.