Low Field Magnetic Stimulation (LFMS) in Subjects With Treatment-Resistant Depression (TRD)

Study Overview
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Brief Summary
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The purpose of this study is to compare the relative effectiveness of 20 and 60 minutes of Low-Field Magnetic Stimulation in relieving symptoms in patients with major depression who are treatment resistant.

Detailed Description
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The primary objective of this study: To compare the relative efficacy, as measured by a change in the 6-item Hamilton Rating Scale for Depression (HAM-D6), of 20 and 60 minutes of LFMS compared to sham (placebo) in subjects with treatment resistant depression (TRD). Secondary objectives: To determine if subjects with TRD may respond to 120 minutes of LFMS. To determine the persistence of response to LFMS therapy during the observation period. To evaluate the safety and tolerability of LFMS.

Official Title
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A Phase 2 Multicenter, Double-Blind, Placebo-Controlled, Dose Optimization Study of Low Field Magnetic Stimulation (LFMS) in Subjects With Treatment-Resistant Depression (TRD)

Conditions
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Depression, Depressive Disorder, Depressive Disorder, Treatment-resistant, Depressive Disorder, Major

Intervention / Treatment
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* Device: LFMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (Key) Meets the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5) criteria for Major Depressive Disorder (MDD), as determined by psychiatric evaluation. Has TRD of the current MDE, as assessed at the site by the Massachusetts General Hospital/Antidepressant Treatment Response Questionnaire (MGH/ATRQ). On an adequate dose of one antidepressant therapy (ADT) for at least eight weeks prior to the screening visit (Visit 1). The ADT dose must be stable for at least four weeks prior to the screening visit (Visit 1). Subjects must be willing to remain on the same stable dose of ADT upon signing the informed consent form until the end of the treatment observation period (end of Week 2) and, where possible, to the end of study participation Exclusion Criteria: (Key) Have failed four or more lifetime adequate ADT treatment regimens (including the ongoing ADT for the current MDE). Have been treated with adjunctive antipsychotic medication with an antidepressant for at least two weeks during the current depressive episode. Are deemed to be at significant risk for suicidal behavior Are unable to lie on their back for the duration of study treatment Have a lifetime history of: Delirium, dementia, amnestic, or other cognitive disorder; Schizophrenia or any psychotic disorder, based on the Structured Clinical Interview for DSM-5 Axis I Disorders Patient Edition (SCID-I/P); Bipolar I or II disorder, based on the SCID-I/P. Have a current DSM-5 diagnosis at the screening visit (Visit 1) of: An eating disorder active within the 12 months prior to the screening visit (Visit 1); Comorbid anxiety disorders that predominate over MDD, as assessed by the investigator; Alcohol or substance use disorder active within the 12 months prior to the screening visit (Visit 1); Clinically significant DSM-5 Axis II disorder. Have ever received electroconvulsive therapy, vagal nerve stimulation, deep brain stimulation or repetitive transcranial magnetic stimulation. Have a non-removable programmable device or appliance such as cardiac pacemakers or cochlear implants. Have any non-removable ferromagnetic implants, or conductive or other magnetic sensitive materials present in the head or neck . Have a lifetime history of seizures or clinically significant electroencephalography abnormalities. A history of childhood febrile seizures is permitted.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: LFMS Sham<br>For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered. Low field magnetic stimulation (no magnetic field for sham) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. | Device: LFMS<br>* Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.<br>* Other names: Low Field Magnetic Stimulation;|
| Active Comparator: LFMS 20 minutes<br>LFMS 20 minutes + Sham 40 min.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. | Device: LFMS<br>* Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.<br>* Other names: Low Field Magnetic Stimulation;|
| Active Comparator: LFMS 60 minutes<br>LFMS 60 minutes.Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. | Device: LFMS<br>* Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.<br>* Other names: Low Field Magnetic Stimulation;|
| Other: LFMS 120 min<br>Week 2 subjects may be re-randomized to receive LFMS 120 minutes. Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. | Device: LFMS<br>* Low field magnetic stimulation (1 kilohertz oscillating magnetic field) will be administered using a portable tabletop device capable of generating time-varying electromagnetic fields of LFMS. For sham therapy, the device will be on; however, no magnetic field stimulation will be delivered.<br>* Other names: Low Field Magnetic Stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) Total Score. | Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from baseline: mean score at Week 1 Day 4 minus mean score at baseline. Week 1 Day 4 : Change from baseline to the end of the efficacy period ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) total score .Responders at Day 4 will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders at Day 4. Each patient's total score is his/her own reference for determining a decrease of 50% or more. | Week 1 Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Day 4 in HAM-D6 Total Score at Day 11 for Week 1 Non-responders: Response to 120 Minutes LFMS | Hamilton Rating Scales for Depression were designed to measure the severity of depressive symptoms in subjects with primary depressive illness. HAM-D6 is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 and all others are scored 0 to 4. Total score ranges from 0 to 22; higher score indicates more depression. Change from Day 11: mean score at Week 2 Day 11 minus mean score at Day 4. To determine if subjects with TRD who are non-responders to 0, 20 or 60 minutes of LFMS on Day 4 may respond to 120 minutes of LFMS at the end of Day 11. Responders will be defined as those subjects who achieve a decrease in HAM-D6 total score of 50% or more compared to baseline (Day 1, Week 1). All other subjects will be deemed to be non-responders. Each patient's total score is his/her own reference for determining a decrease of 50% or more. | Day 11 (Week 2) | 
| Day 4 Responders: Persistence of Effect Based on Pre-specified HAM-D6 Total Score | To determine the persistence of response to LFMS therapy during a four-week follow-up period in subjects who were responders at Day 4. Persistence of response was achieved if during Week 2 post baseline visits and follow-up visits subjects' 6-item Hamilton Rating Scale for Depression (HAM-D6) total scores were lower than or equal to 50% of the baseline ( Day1 Week1) scores. Non-responder imputation method was used where missing post-baseline dichotomous (yes or no) were imputed as non-responder. Logistic regression model used to compare treatment groups for each visit, where the model considers the treatment, age and gender as covariates. | Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LFMS, Depression, Major depression, Low-field magnetic stimulation