MDDMDDNCT04279522
The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD)
A study testing Relivion®DP- Active in people with MDD, run by Neurolief Ltd. at 13 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- MDD
- What is being tested?
- Relivion®DP- Active
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 31 Aug 2021to 7 Jun 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
- Participation in a previous study with the Relivion®DP or the Relivion® device.
- Treatment with Transcranial Magnetic Stimulation (TMS) in the past 6 months.
- Current treatment with any other approved or investigational brain stimulation therapies (i.e. Vagus or trigeminal nerve Stimulation, tDCS, TES).
- 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.
- Subject having received Botox treatment in the head or neck region within 90 days prior to study enrollment.
- Subject having received supraorbital or occipital nerve blocks within 1 month prior to enrollment.
- Head circumference smaller than 51 centimeters or larger than 60 centimeters.
- 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.
- Subjects participating in other clinical trials evaluating experimental treatments or procedures.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States12 sites
Sheppard Prat Health system
Baltimore, Maryland, 21204
University of North Carolina, Department of Psychiatry
Chapel Hill, North Carolina, 27514
MUSC Institute of Psychiatry
Charleston, South Carolina, 29425
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, 60611
Brain Health Consultants and TMS Center
Houston, Texas, 77046
Kadima Neuropsychiatry Institute
La Jolla, California, 92037
UCLA Semel Institute for Neuroscience and Behaviour
Los Angeles, California, 90024
San Marcus Research Clinic
Miami Lakes, Florida, 33014
University of Minnesota
Minneapolis, Minnesota, 55416
Butler Hospital/Brown University
Providence, Rhode Island, 02906
VA Providence Healthcare System
Providence, Rhode Island, 02908
K2 Medical Research Tampa
Tampa, Florida, 33607
About this study
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.
Read more
The study will include the following stages:
- Screening, Eligibility evaluation and Randomization to Relivion®DP vs. Sham control (1:1 randomization) (Baseline - Day 0).
- Daily treatment period: Active/Sham (Group A/B) treatment protocol (Baseline to end of 8 weeks).
- 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.
Read the 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.
- Conditions
- MDD
- Being tested
- Relivion®DP- Active, Relivion®DP- Sham
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Relivion®DP- ActiveDevice
Relivion®DP- Active stimulation device
Relivion®DP- ShamDevice
Relivion®DP- Sham stimulation device
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - active stimulation | Experimental | Not described Receives: Device: Relivion®DP- Active |
| Group 2 - sham stimulation | Placebo comparator | Not described Receives: Device: Relivion®DP- Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks from treatment initiation
Secondary outcomes (3)
Percentage of Responder Participants
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.
Measured: 8 weeks from treatment initiation
Percentage of Subjects Achieving Remission
Proportion of subjects achieving remission- defined as the percent of subjects with HDRS17 score≤7 at 8 weeks post treatment initiation
Measured: 8 weeks from treatment initiation
Mean Change in Depressive Symptoms, Measured by MADRS Total Score
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.
Measured: 8 weeks from treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start31 Aug 2021
- Primary completion7 Jun 2024
- Study completion7 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MDDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurolief Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Linda Carpenter, MD, Principal investigator, Butler Hospital, Brown Department of Psychiatry and Human, RI, USA Behavior,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04279522
- Sponsor's protocol ID
- SP-201-MOOD
- Acronym
- MDD
- Status last verified
- Jul 2025
- First submitted
- 19 Feb 2020
- Last updated
- 12 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The MOOD Study - External Combined Occipital and Trigeminal Nerve Stimulation (eCOT-NS) for the Treatment of Major Depressive Disorder (MDD)
- ClinicalTrials.gov ID
- NCT04279522
- Acronym / sponsor ID
- MDD / SP-201-MOOD
- Conditions
- MDD
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Neurolief Ltd.Industry (pharma, biotech, devices)
- Study start
- 31 Aug 2021 (actual)
- Primary completion
- 7 Jun 2024 (actual)
- Study completion
- 7 Jun 2024 (actual)
- First posted
- 21 Feb 2020 (actual)
- Results
- Posted 12 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Screening, Eligibility evaluation and Randomization to Relivion®DP vs. Sham control (1:1 randomization) (Baseline - Day 0).
- Daily treatment period: Active/Sham (Group A/B) treatment protocol (Baseline to end of 8 weeks).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - active stimulation | Experimental | Device: Relivion®DP- Active |
| Group 2 - sham stimulation | Placebo comparator | Device: Relivion®DP- Sham |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Males and females 18-70 years of age:
- 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):
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Relivion®DP- ActiveRelivion®DP- Active stimulation device | Device | Group 1 - active stimulation |
| Relivion®DP- ShamRelivion®DP- Sham stimulation device | Device | Group 2 - sham stimulation |
Primary outcome
Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score
Time frame: 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.
3 secondary outcomes
Percentage of Responder Participants
Time frame: 8 weeks from treatment initiation
Percentage of Subjects Achieving Remission
Time frame: 8 weeks from treatment initiation
Mean Change in Depressive Symptoms, Measured by MADRS Total Score
Time frame: 8 weeks from treatment initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda Carpenter, MD principal investigator
Butler Hospital, Brown Department of Psychiatry and Human, RI, USA Behavior,
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Relivion®DP- Active in people with MDD, run by Neurolief Ltd. at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Depressive Symptoms, Measured by HDRS17 Total Score (time frame: 8 weeks from treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.