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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04279522

Acronym

MDD

Enrollment

124

Registered

2020-02-21

Start date

2021-08-31

Completion date

2024-06-07

Last updated

2025-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

MDD

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. Screening, Eligibility evaluation and Randomization to Relivion®DP vs. Sham control (1:1 randomization) (Baseline - Day 0). 2. Daily treatment period: Active/Sham (Group A/B) treatment protocol (Baseline to end of 8 weeks). 3. Open label phase: Active treatment period of additional 8 weeks. After completion of the open label period the subject's participation in the study will be over.

Detailed description

The study will include the following study visits & phases: * Visit 1- Screening (Day (-14)-0) - Screening & Preliminary Eligibility Assessment. * Visit 2- Baseline (Day (-4)-0) - Eligibility, baseline assessment, Randomization to Relivion®DP vs. Sham control (1:1 randomization) and training. * Double blind phase (Day 0 to day 56±7)- 5-7 days a week treatment: Active/Sham (Group A/B) treatment protocol. * Visit 3- Follow Up Visit (day 28±7)- MDD assessment. * Visit 4- End of Double-Blind phase (day 56±7)- MDD assessment. * Open label phase- Active treatment period: According to HDRS response in DB phase, in between Maintenance treatment 3-4 times a week and up to 5-7 days a week of intensified treatment (Day 56±7 to day 112±7) * Visit 5- follow up visit (day 84±7) - MDD assessment. * Visit 6- End of study (day 112±7)- MDD assessment and end of study.

Interventions

DEVICERelivion®DP- Active

Relivion®DP- Active stimulation device

DEVICERelivion®DP- Sham

Relivion®DP- Sham stimulation device

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

1. Males and females 18-70 years of age: 1. Up to 124 randomized subjects aged 22-70 2. Up to 36 randomized subjects aged 18-21 2. Primary diagnosis of unipolar major depressive disorder by DSM-V criteria. 3. Current MDD episode lasts up to three years. 4. Score on the Hamilton Depression Rating Scale (HDRS21) ≥ 20 5. 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). 6. 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. 7. 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. 8. Subject is able to provide written Informed Consent and is capable of complying with the specified study requirements, as determined by the Investigator. 9. Subject has cognitive and/or motor skills needed to operate a smartphone and can be contacted by phone, as determined by the Investigator.

Exclusion criteria

1. History of intracranial surgery. 2. 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. 3. 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. 4. Skin lesion, scars, or inflammation at the region of the stimulating electrodes. 5. 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. 6. Pregnancy or Lactation. 7. Women of reproductive age not using a reliable contraceptive method as determined by the Investigator. 8. 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. 9. 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 10. 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. 11. 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. 12. 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. 13. Subjects currently (past month) meeting diagnostic criteria for Obsessive-Compulsive Disorder or post-traumatic stress disorder and that is their primary diagnosis. 14. 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. 15. 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. 16. Participation in a previous study with the Relivion®DP or the Relivion® device. 17. Treatment with Transcranial Magnetic Stimulation (TMS) in the past 6 months. 18. Current treatment with any other approved or investigational brain stimulation therapies (i.e. Vagus or trigeminal nerve Stimulation, tDCS, TES). 19. Failure to receive clinical benefit from an adequate trial of ECT in the current or a past depressive episode in the opinion of the Investigator. 20. Subject having received Botox treatment in the head or neck region within 90 days prior to study enrollment. 21. Subject having received supraorbital or occipital nerve blocks within 1 month prior to enrollment. 22. Head circumference smaller than 51 centimeters or larger than 60 centimeters. 23. Current neurological condition or disease which, in the opinion of the investigator, is likely to manifest a depressive syndrome or symptoms that would substantially confound the diagnosis or serial assessment of major depressive disorder. 24. Subjects participating in other clinical trials evaluating experimental treatments or procedures.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score	8 weeks from treatment initiation	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.

Secondary

Measure	Time frame	Description
Percentage of Responder Participants	8 weeks from treatment initiation	Proportion of responder subjects- defined as the percent of subjects achieving at least 50% reduction from baseline in their HDRS17 scale 8 weeks post Relivion®DP treatment initiation.
Percentage of Subjects Achieving Remission	8 weeks from treatment initiation	Proportion of subjects achieving remission- defined as the percent of subjects with HDRS17 score≤7 at 8 weeks post treatment initiation
Mean Change in Depressive Symptoms, Measured by MADRS Total Score	8 weeks from treatment initiation	Mean change in depressive symptoms, measured by MADRS total score, from baseline to week-8 post treatment initiation. The MADRS stands for the Montgomery-Åsberg Depression Rating Scale. It is a clinician-administered tool used to assess the severity of depressive symptoms, particularly in clinical trials and psychiatric evaluations. Contains 10 items, each scored from 0 to 6, with a total possible score ranging from 0 to 60. Higher scores indicate more severe depression.

Other

Measure	Time frame	Description
Mean Change in Quick Inventory of Depressive Symptomatology Self-rated Score	8 weeks from treatment initiation	Mean Change from baseline in total score of the Quick Inventory of Depressive Symptomatology self-rated (QIDS-SR-16) score at 8 weeks post treatment initiation. The QIDS-SR-16 stands for the Quick Inventory of Depressive Symptomatology - Self-Report, 16-item version. It is a self-administered questionnaire designed to assess the severity of depressive symptoms in patients. Total score range: 0 to 27. Higher scores indicate more severe depression.
Mean Change in Depressive Symptoms, Measured by HDRS21 Total Score	8 weeks from treatment initiation	Mean change in depressive symptoms, measured by HDRS21 total score, from baseline to week-8 post Relivion®DP treatment initiation. The HDRS-21, or 21-item Hamilton Depression Rating Scale, is an extended version of the original Hamilton Depression Rating Scale (HDRS17). It is a clinician-administered tool designed to assess the severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD). Total score range: 0 to 64. higher scores indicate more severe depression.
Mean Change in Depressive Symptoms Severity and Improvement Scores	8 weeks from treatment initiation	Mean Change in the severity and improvement scores - Clinical Global Impression scales (CGI-S and CGI-I) at 8 weeks post treatment initiation. he CGI-S (Clinical Global Impression - Severity) and CGI-I (Clinical Global Impression - Improvement) are two components of the CGI scale, a brief, standardized assessment used by clinicians to rate the severity of a patient's illness and their improvement over time, typically in clinical trials and psychiatric practice. both on a Scale of 1 to 7. higher score on the CGI-S indicate more severe depression. Higher score on the CGI-I indicates worsening depression.

Countries

Israel, United States

Participant flow

Participants by arm

Arm	Count
Group 1 - Active Stimulation Relivion®DP- Active: Relivion®DP- Active stimulation device	62
Group 2 - Sham Stimulation Relivion®DP- Sham: Relivion®DP- Sham stimulation device	62
Total	124

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period 1: Double Blind Phase	Lost to Follow-up	0	1
Period 1: Double Blind Phase	Protocol Violation	1	0
Period 1: Double Blind Phase	Withdrawal by Subject	10	8
Period 2: Open Label Phase	Adverse Event	0	1
Period 2: Open Label Phase	Lost to Follow-up	1	1
Period 2: Open Label Phase	Physician Decision	0	3
Period 2: Open Label Phase	Protocol Violation	1	0
Period 2: Open Label Phase	Withdrawal by Subject	2	2

Baseline characteristics

Characteristic	Group 1 - Active Stimulation	Group 2 - Sham Stimulation	Total
Age, Continuous	49.2 Years STANDARD_DEVIATION 13.14	48.1 Years STANDARD_DEVIATION 13.14	48.6 Years STANDARD_DEVIATION 13.1
Number of antidepressant medications with none or insufficient response in the current episode	1.8 Number of antidepressant medications STANDARD_DEVIATION 0.97	1.8 Number of antidepressant medications STANDARD_DEVIATION 0.89	1.8 Number of antidepressant medications STANDARD_DEVIATION 0.93
Race/Ethnicity, Customized African or African-American	2 Participants	3 Participants	5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Asian	2 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized Caucasian	44 Participants	44 Participants	88 Participants
Race/Ethnicity, Customized not reported	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized other	14 Participants	12 Participants	26 Participants
Region of Enrollment Israel	1 participants	2 participants	3 participants
Region of Enrollment United States	61 participants	60 participants	121 participants
Sex: Female, Male Female	43 Participants	46 Participants	89 Participants
Sex: Female, Male Male	19 Participants	16 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 62	0 / 62	0 / 96
other Total, other adverse events	18 / 62	20 / 62	29 / 96
serious Total, serious adverse events	0 / 62	0 / 62	1 / 96

Outcome results

Primary

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.