The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD)

NCT04279522 | Completed Results DMC FDA Device

• 1 other identifier: SP-201-MOOD
• Study Type: interventional
• Target: 124
• Locations: 2 countries
• Sites: 13

Brief Summary

The MOOD study will evaluate the safety and efficacy of a noninvasive, self-administered external Combined Occipital and Trigeminal Neurostimulation (eCOT-NS) treatment for Major Depressive Disorder (Relivion®DP). This is a prospective, multi-center, 2-arm randomized, double-blind, parallel-group, sham-controlled study. The study will include the following stages:

1. 1.Screening, Eligibility evaluation and Randomization to Relivion®DP vs. Sham control (1:1 randomization) (Baseline - Day 0).
2. 2.Daily treatment period: Active/Sham (Group A/B) treatment protocol (Baseline to end of 8 weeks).
3. 3.Open label phase: Active treatment period of additional 8 weeks.

Conditions

MDD

Outcome Measures

Primary Outcomes (1)

• Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score

  Mean change in depressive symptoms, measured by HDRS17 total score, from baseline to week-8 post treatment initiation. The HDRS-17 (17-item Hamilton Depression Rating Scale) is a widely used, clinician-administered questionnaire designed to assess the severity of depressive symptoms. Total score ranges from 0 to 52-higher scores indicate more severe depression.

  8 weeks from treatment initiation

Secondary Outcomes (3)

• Percentage of Responder Participants

  8 weeks from treatment initiation

• Percentage of Subjects Achieving Remission

  8 weeks from treatment initiation

• Mean Change in Depressive Symptoms, Measured by MADRS Total Score

  8 weeks from treatment initiation

Other Outcomes (3)

• Mean Change in Depressive Symptoms Severity and Improvement Scores

  8 weeks from treatment initiation

• Mean Change in Quick Inventory of Depressive Symptomatology Self-rated Score

  8 weeks from treatment initiation

• Mean Change in Depressive Symptoms, Measured by HDRS21 Total Score

  8 weeks from treatment initiation

Study Arms (2)

Group 1 - active stimulation

EXPERIMENTAL

Device: Relivion®DP- Active

Group 2 - sham stimulation

PLACEBO COMPARATOR

Device: Relivion®DP- Sham

Interventions

Relivion®DP- Active DEVICE

Relivion®DP- Active stimulation device

Group 1 - active stimulation

Relivion®DP- Sham DEVICE

Relivion®DP- Sham stimulation device

Group 2 - sham stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18-70 years of age:
• Up to 124 randomized subjects aged 22-70
• Up to 36 randomized subjects aged 18-21
• Primary diagnosis of unipolar major depressive disorder by DSM-V criteria.
• Current MDD episode lasts up to three years.
• Score on the Hamilton Depression Rating Scale (HDRS21) ≥ 20
• Symptoms of current major depressive episode that, as determined by the Investigator, for the current episode and according to the Antidepressant Treatment Resistance Form (ATRF) or Antidepressant Treatment Intolerance Form (ATIF):
• Did not respond or have insufficiently responded by less than 50% improvement; dose and duration defined \& rated at minimum confidence level 3 on the ATRF;
• Did not respond or has insufficiently responded to at least one but no more than four adequate trials of antidepressant medications (4 ≥ ATRF ≥1) or
• Did not respond or has insufficiently responded due to poor tolerability to at least two inadequate antidepressant medication trials (ATIF ≥2).
• Subject must be on at least one (1) antidepressant medication (minimum therapeutic dose not required if tolerability precluded further dose titration) and is willing to remain on the same daily dose of antidepressant medication(s) for a minimum of 28 days prior to randomization and thereafter for the duration of the study.
• For subjects receiving current depression focused psychotherapy: psychotherapy initiated at least 1 month prior to baseline visit with a stable frequency of visits regimen, in the opinion of the Investigator.
• Subject is able to provide written Informed Consent and is capable of complying with the specified study requirements, as determined by the Investigator.
• Subject has cognitive and/or motor skills needed to operate a smartphone and can be contacted by phone, as determined by the Investigator.

You may not qualify if:

• History of intracranial surgery.
• Current denervation in one or more of the following: the supraorbital or supratrochlear branches of the trigeminal nerve, or the greater occipital branch of the occipital nerve.
• An implanted neurostimulators or any implanted metallic or electronic device in the head, a cardiac pacemaker or an implanted or wearable defibrillator, except for dental implants.
• Skin lesion, scars, or inflammation at the region of the stimulating electrodes.
• Subjects with a history of traumatic brain injury (TBI), defined as a disruption in the normal function of the brain that can be caused by a bump, blow, or jolt to the head, or penetrating head injury, within 3 months of study enrollment.
• Pregnancy or Lactation.
• Women of reproductive age not using a reliable contraceptive method as determined by the Investigator.
• In the opinion of the Investigator, subjects with a psychiatric history consistent with, suspicious for, or diagnostic of, bipolar depression or depression associated with psychosis.
• Borderline personality disorder, defined by DSM-V criteria, that in the judgement of the Investigator is likely to complicate the assessment of clinical response to study treatments or limits the patient's ability to comply with study procedures
• Subjects who, within one (1) year of study enrollment, have a history consistent with, suspicious for or diagnostic of, any of the following: psychosis, psychotic disorder, schizophrenia or schizoaffective disorder, in the opinion of the Investigator.
• Subjects who demonstrate or have a history of any cognitive disorder or impairment, memory loss, dementia, confusion or delirium that, in the opinion of the Investigator, may compromise the integrity of the study data or impact the ability of the subject to comply with the study requirements.
• Past 12 months active suicidal intent or plan as defined by a "yes" answer to Q4 or Q5 on the Columbia-Suicide Severity Rating Scale, (C-SSRS) or with a history of suicide attempt in the past twelve months.
• Subjects currently (past month) meeting diagnostic criteria for Obsessive-Compulsive Disorder or post-traumatic stress disorder and that is their primary diagnosis.
• Subjects meeting the DSM-V criteria for alcohol use disorder or other substance use disorder (not including tobacco/nicotine) within six (6) months prior to study enrollment.
• The subject has any past or present medical condition, disease, illness, disorder or injury that, in the opinion of the Investigator, may reduce or hinder the subject's ability to fully comply with all study requirements for the duration of the study or may confound the integrity of the study data.

Sponsors & Collaborators

• Neurolief Ltd.: lead

Study Sites (13)

Kadima Neuropsychiatry Institute

La Jolla, California, 92037, United States

Location

UCLA Semel Institute for Neuroscience and Behaviour

Los Angeles, California, 90024, United States

Location

San Marcus Research Clinic

Miami Lakes, Florida, 33014, United States

Location

K2 Medical Research Tampa

Tampa, Florida, 33607, United States

Location

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Sheppard Prat Health system

Baltimore, Maryland, 21204, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55416, United States

Location

University of North Carolina, Department of Psychiatry

Chapel Hill, North Carolina, 27514, United States

Location

Butler Hospital/Brown University

Providence, Rhode Island, 02906, United States

Location

VA Providence Healthcare System

Providence, Rhode Island, 02908, United States

Location

MUSC Institute of Psychiatry

Charleston, South Carolina, 29425, United States

Location

Brain Health Consultants and TMS Center

Houston, Texas, 77046, United States

Location

Ichilov Medical Center

Tel Aviv, Israel

Location

Results Point of Contact

• Title: Yaron Gruper, Director of Clinical affairs
• Organization: Neurolief Ltd.

Yaron.Gruper@neurolief.com

+972-544330712

Study Officials

• Linda Carpenter, MD

  Butler Hospital, Brown Department of Psychiatry and Human, RI, USA Behavior,

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: February 21, 2020
• Study Start: August 31, 2021
• Primary Completion: June 7, 2024
• Study Completion: June 7, 2024
• Last Updated: August 12, 2025
• Results First Posted: August 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1); US (12)