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

• ClinicalTrials.gov Identifier: NCT02452892
• Recruitment Status: Completed
• First Posted: May 25, 2015
• Results First Posted: December 5, 2017
• Last Update Posted: December 5, 2017
• Sponsor: Tal Medical, Inc.
• Information provided by (Responsible Party): Tal Medical, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Depression; Depressive Disorder; Depressive Disorder, Treatment-resistant; Depressive Disorder, Major	Device: LFMS	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter, Double-Blind, Placebo-Controlled, Dose Optimization Study of Low Field Magnetic Stimulation (LFMS) in Subjects With Treatment-Resistant Depression (TRD)
• Study Start Date: September 2015
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: October 2016

Arms and Interventions

Arm	Intervention/treatment
Sham Comparator: LFMS Sham; 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; 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.; Other Name: Low Field Magnetic Stimulation
Active Comparator: LFMS 20 minutes; 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; 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.; Other Name: Low Field Magnetic Stimulation
Active Comparator: LFMS 60 minutes; 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; 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.; Other Name: Low Field Magnetic Stimulation
LFMS 120 min; 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; 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.; Other Name: Low Field Magnetic Stimulation

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to ( Day 4) in the 6-item Hamilton Rating Scale for Depression (HAM-D6) Total Score. [ Time Frame: Week 1 Day 4 ]

   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.

Secondary Outcome Measures :

1. Change From Day 4 in HAM-D6 Total Score at Day 11 for Week 1 Non-responders: Response to 120 Minutes LFMS [ Time Frame: Day 11 (Week 2) ]

   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.

2. Day 4 Responders: Persistence of Effect Based on Pre-specified HAM-D6 Total Score [ Time Frame: Day 42 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

  1. Delirium, dementia, amnestic, or other cognitive disorder;
  2. Schizophrenia or any psychotic disorder, based on the Structured Clinical Interview for DSM-5 Axis I Disorders Patient Edition (SCID-I/P);
  3. Bipolar I or II disorder, based on the SCID-I/P.

• Have a current DSM-5 diagnosis at the screening visit (Visit 1) of:

  1. An eating disorder active within the 12 months prior to the screening visit (Visit 1);
  2. Comorbid anxiety disorders that predominate over MDD, as assessed by the investigator;
  3. Alcohol or substance use disorder active within the 12 months prior to the screening visit (Visit 1);
  4. 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.

Contacts and Locations

Locations

United States, California

CNS Trials

Garden Grove, California, United States, 92845

Synergy Escondido

Lemon Grove, California, United States, 91945

Pacific Trials Partners

Oakland, California, United States, 94612

United States, Florida

Sarkis Clinical Trials

Gainesville, Florida, United States, 32607

CNS Healthcare

Jacksonville, Florida, United States, 32256

Segal Institute

Lauderhill, Florida, United States, 33319

United States, Georgia

Institute for Advanced Medical Research

Alpharetta, Georgia, United States, 30005

Radiant Research

Atlanta, Georgia, United States, 30328

United States, Ohio

Neurobehavioral-Clinical Research

Canton, Ohio, United States, 44718

Midwest Clinical

Dayton, Ohio, United States, 45417

United States, Texas

Future Search Trials

Dallas, Texas, United States, 75231

United States, Washington

Northwest Clinical Research Center

Bellevue, Washington, United States, 98007

Sponsors and Collaborators

Tal Medical, Inc.

Investigators

• Study Chair: Atul Pande, MD; Tal Medical

More Information

• Responsible Party: Tal Medical, Inc.
• ClinicalTrials.gov Identifier: NCT02452892
• Other Study ID Numbers: TAL-02-007
• First Posted: May 25, 2015
• Results First Posted: December 5, 2017
• Last Update Posted: December 5, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Tal Medical, Inc.:

Depression; Major depression; Low-field magnetic stimulation; LFMS

Additional relevant MeSH terms:

Disease; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Pathologic Processes; Behavioral Symptoms; Mood Disorders; Mental Disorders