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

A Prospective, Multicenter, Double-Blind, Sham-Controlled Adaptive Design Study to Confirm the Safety and Efficacy of NEST sTMS in Subjects With Major Depressive Disorder Who Have Not Responded to at Least One Antidepressant Medication in the Current Episode

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Depression; Depressive Disorder, Major; Major Depressive Disorder; Depressive Episode
• Intervention / Treatment: Device: Synchronized Transcranial Magnetic Stimulation (sTMS); Device: Sham Stimulation

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).

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Kadima Neuropsychiatry Institute
    • Los Angeles, California, United States, 90024
      • UCLA Westwood - Semel Institute for Neuroscience and Human Behavior
    • Stanford, California, United States, 94305
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Sheppard Pratt Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University/Barnes Jewish Hospital
  • New York
    • New York, New York, United States, 10016
      • New York University
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Laureate Institute for Brain Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77046
      • Brain Health Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active sTMS; Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.	Device: Synchronized Transcranial Magnetic Stimulation (sTMS); sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).
SHAM_COMPARATOR: Sham Stimulation; Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.	Device: Sham Stimulation; Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population	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.	Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment	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.	Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population	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.	Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
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	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.	Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments	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.	Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12
Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population	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.	Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12

Collaborators and Investigators

• Sponsor: Wave Neuroscience

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 27, 2017
• Primary Completion (ACTUAL): March 1, 2019
• Study Completion (ACTUAL): June 1, 2019

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (ACTUAL): September 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; TMS; sTMS
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: NND-3002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No