Adaptive Design Study of NEST sTMS in Subjects With Major Depressive Disorder

Not Applicable

Completed

Conditions: Depressive Episode
Depression
Major Depressive Disorder
Depressive Disorder
Depressive Disorder, Major

Interventions: Device: Sham Stimulation
Device: Synchronized Transcranial Magnetic Stimulation (sTMS)

Registration Number: NCT03288714

Lead Sponsor: Wave Neuroscience

Brief Summary: This is a double-blind, sham controlled, multi-center study to confirm the safety and efficacy of synchronized transcranial magnetic stimulation (sTMS) for the treatment of patients currently experiencing an episode of depression who have failed to respond to at least one (1) antidepressant medication. Patients will be randomly assigned to either active or sham therapy and will undergo daily treatments for a period of time. Following completion of blinded treatments, patients may be eligible for a course of open label treatments.

Detailed Description: Prospective, randomized, double-blind, sham-controlled, parallel group adaptive design study to confirm the safety and efficacy of sTMS in subject with Major Depressive Disorder (MDD) who have not responded to at least one antidepressant medication in the current episode. MDD was diagnosed according to DSM-IV criteria rendered by structured interview using the Mini International Neuropsychiatric Interview (MINI).

Subjects must have discontinued any antidepressant medication a minimum of 1 week prior to initiation of treatment with the active sTMS or sham device. Following wash-out of the antidepressant medication, an additional evaluation was performed to determine whether the protocol eligibility criteria were met before randomization and treatment.

Randomized subjects were treated 5 days per week for 6 weeks. Subjects who completed 6 weeks of double-blind treatment may have been eligible to receive up to 6 weeks of open-label treatment as clinically indicated during the follow-up phase of the study.

Follow-up evaluation visits were conducted during those six weeks, with frequency of the visits determined by the treatment choice during that time frame (open label subjects had weekly evaluation visits for 6 weeks).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 121

Inclusion Criteria

Current episode of Major Depressive Disorder
Inadequate response to at least one antidepressant medication in the current episode (Treatment Resistant Depression)
Investigator able to identify IAF using EEG
Willingness and ability to adhere to treatment schedule (5 treatments per week for six weeks)

Exclusion Criteria

Unable to unwilling to give informed consent
Diagnosed with excluded conditions or treatment histories
Currently hospitalized due to severity of depression symptoms
Use of prohibited medications (as defined by protocol) within specified time frame of randomization
Use of certain cardiac devices
Use of certain intracranial devices
Currently pregnant or unwilling to practice acceptable means of birth control, and women who are breastfeeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham Stimulation	Sham Stimulation	Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.
Active sTMS	Synchronized Transcranial Magnetic Stimulation (sTMS)	Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.

Primary Outcome Measures

Name	Time	Method
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population	Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6	Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.

Secondary Outcome Measures

Name	Time	Method
Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment	Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6	Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population	Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6	Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups. The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression.
Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz	Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6	Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments	Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12	Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population	Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12	Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups. The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.

Trial Locations

Locations (14): Kadima Neuropsychiatry Institute
🇺🇸
La Jolla, California, United States
Washington University/Barnes Jewish Hospital
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Saint Louis, Missouri, United States
Butler Hospital
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Providence, Rhode Island, United States
Stanford University
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Stanford, California, United States
Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States
Mayo Clinic
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Rochester, Minnesota, United States
Brain Health Consultants
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Houston, Texas, United States
UCLA Westwood - Semel Institute for Neuroscience and Human Behavior
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Los Angeles, California, United States
Sheppard Pratt Health System
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Baltimore, Maryland, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
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Dallas, Texas, United States
Laureate Institute for Brain Research
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Tulsa, Oklahoma, United States
Emory University
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Atlanta, Georgia, United States
New York University
🇺🇸
New York, New York, United States