Major Depressive DisorderMaitr-DeNCT06938841
Maintenance rTMS for Depression (Maitr-De)
A study testing Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS: and Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS: in people with Major Depressive Disorder and Treatment Resistant Depression, run by University of California, San Diego at 3 sites in 2 countries.
Trial summary
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for treatment-resistant depression (TRD), yet substantial uncertainties persist regarding its efficacy as a maintenance treatment. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Major Depressive Disorder, Treatment Resistant Depression
- What is being tested?
- Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS: and Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Apr 2025to 31 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- They met criteria for a DSM-5 diagnosis of a Major Depressive Episode (MDE) during the index episode of depression for which they have received an acute rTMS treatment course.
- Meet criteria for either response or remission from their initial depressive illness. The MINI assessment timeline will be adjusted to allow scoring of illness symptoms prior to rTMS response. Response to acute course of treatment is defined as either a MADRS score of <10, or a MADRS score of 10-19, plus evidence of having met response criteria on either the MADRS or another structured depression rating scale. The response is defined as a >50% reduction in the total score from the start to the end of treatment.
- Their initial rTMS treatment course must have consisted of at least 15 rTMS treatment sessions.
- People between the ages of 18 and 80 at the time of screening. A written statement from the referring physician will be required to confirm that the participant demonstrates the capacity to consent.
- Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during TMS-EEG assessments and iTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- In good general health, as evidenced by medical history.
- Agreement to adhere to Lifestyle Considerations throughout study duration.
- If a person of child-bearing potential is: must take a pregnancy test at the screening visit, with results confirmed as negative by study staff
Who cannot join
- 1. Pregnancy 2. History of or current psychotic disorder or depression with psychotic features 3. Severe borderline personality disorder based on clinical assessment. 4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder 5. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal 6. Clinically significant suicidal ideation with plan 7. Any history of ECT (greater than 8 sessions) without a clinical meaningful response in the current episode.
- 8. Recent (during the current depressive episode) or concurrent use of rapid-acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days 9. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma 10. Untreated or insufficiently treated endocrine disorder. 11. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) 12. Treatment with an investigational drug or other intervention within the study period 13. The patient experiences a relapse between baseline and screening, defined as a moderate depression (MADRS >=20) and a 25% increase from screening to baseline 14. Require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any anticonvulsant (with the exception of Gabapentin, pregabalin, and lamotrigine).
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
United States2 sites, 2 recruiting
- Recruiting
Weill Cornell Medicine
New York, New York, 10065
Megan Johnson, 646-962-2900, tmsinfo@med.cornell.edu
Conor M Liston, PhD, MD
- Recruiting
University of California, San Diego
San Diego, California, 92127
Bianca Bacio, 858-657-6152, bbacio@health.ucsd.edu
Zafiris J Daskalakis, MD. Ph.D.
Australia1 site, 1 recruiting
- Recruiting
Australian National University
Canberra, Australian Capital Territory, 2601
Shona Brinley, shona.brinley@anu.edu.au
Paul B Fitzgerald, MPM, PhD
About this study
Official title: Maintaining the Acute Therapeutic Effect of rTMS in Treatment-Resistant Depression (Maitr-De)
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for treatment-resistant depression (TRD), yet substantial uncertainties persist regarding its efficacy as a maintenance treatment. This prospective study seeks to investigate the efficacy of maintenance rTMS in individuals with TRD who have previously responded to an acute course of rTMS. In the R61 phase of the study, we will recruit 75 participants across three study sites, the University of California San Diego, Weill Cornell Medicine, and Australian National University, into a double-blind, three-arm maintenance treatment trial. In this trial, participants will be randomized to receive either standard maintenance rTMS, clustered maintenance rTMS, or sham maintenance rTMS for a duration of 6 months. Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period. We will also assess changes in depressive symptom severity using clinical scales, including the Montgomery-Asberg Depression Rating Scale (MADRS) as a secondary outcome measure. It is hypothesized that stimulation with clustered maintenance rTMS will demonstrate superiority in sustaining DLPFC-SGC connectivity compared with standard maintenance rTMS and sham maintenance rTMS
- Being tested
- Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS:, Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:, Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMS
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS:Device
In this approach, patients who were treated with rTMS five days per week during their acute episode receive less frequent treatments during a taper period (for example treatment three days per week followed by two sessions per week) with a gradual transition into a maintenance schedule. For example, the maintenance schedule might begin with a single weekly session for one or two months and then the intensity is reduced to one session every two weeks (and possibly then one session every three or four weeks).
Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:Device
Clustered maintenance rTMS typically involves around 4 TMS sessions applied over 2 days, at 1-month intervals. Our team initially developed this approach based upon preclinical TMS studies (for example (Maeda et al. 2000)) suggesting that rTMS treatment effects may accumulate when applied over multiple sessions in a shorter period of time (Maeda et al. 2000).
Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMSDevice
Sham treatment will be administered as either standard or clustered maintenance rTMS for 6 months period using a sham coil. The intervention target will be located via a Brainsight TMS Navigator (Brainsight, Montreal, Canada). For safety reasons, the individual TMS intensity will be limited to 130% of the individual resting motor threshold.
| Study group | Role | What they receive |
|---|---|---|
| Clustered maintenance rTMS | Experimental | Clustered maintenance treatment involves administering four sessions of rTMS over a two-day span, conducted once per month for six months. Receives: Device: Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS: |
| Standard maintenance rTMS: | Active comparator | Standard maintenance rTMS involves a course of rTMS with once-weekly sessions for 6 months. Receives: Device: Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS: |
| sham maintenance rTMS | Placebo comparator | Somatosensory-matched placebo rTMS is delivered according to either standard or clustered maintenance schedules over a six-month period (50/50% allotment). Patient's maintenance protocol parameters will otherwise mirror those used during their acute treatment with identical cortical targets, stimulation intensity, frequency, and duration. Sham TMS-EEG will be conducted by rotating the coil 90 degrees while maintaining contact with the scalp. This standard practice prevents current induction while replicating the auditory click associated with TMS, ensuring comparable EEG recordings Receives: Device: Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aim: To evaluate the effects of two active rTMS maintenance treatments (i.e., standard and clustered) compared to sham maintenance rTMS on DLPFC-SGC connectivity.
Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period
Measured: 6-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2025
- Study start1 Apr 2025
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Zafiris Daskalakis, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06938841
- Sponsor's protocol ID
- 811708
- Acronym
- Maitr-De
- Status last verified
- Apr 2026
- First submitted
- 14 Apr 2025
- Last updated
- 29 Apr 2026
- Results posted
- No
- 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 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maintaining the Acute Therapeutic Effect of rTMS in Treatment-Resistant Depression (Maitr-De)
- ClinicalTrials.gov ID
- NCT06938841
- Acronym / sponsor ID
- Maitr-De / 811708
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 22 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for treatment-resistant depression (TRD), yet substantial uncertainties persist regarding its efficacy as a maintenance treatment. This prospective study seeks to investigate the efficacy of maintenance rTMS in individuals with TRD who have previously responded to an acute course of rTMS. In the R61 phase of the study, we will recruit 75 participants across three study sites, the University of California San Diego, Weill Cornell Medicine, and Australian National University, into a double-blind, three-arm maintenance treatment trial. In this trial, participants will be randomized to receive either standard maintenance rTMS, clustered maintenance rTMS, or sham maintenance rTMS for a duration of 6 months. Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period. We will also assess changes in depressive symptom severity using clinical scales, including the Montgomery-Asberg Depression Rating Scale (MADRS) as a secondary outcome measure. It is hypothesized that stimulation with clustered maintenance rTMS will demonstrate superiority in sustaining DLPFC-SGC connectivity compared with standard maintenance rTMS and sham maintenance rTMS
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Clustered maintenance rTMS | Experimental | Device: Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:Clustered maintenance treatment involves administering four sessions of rTMS over a two-day span, conducted once per month for six months. |
| Standard maintenance rTMS: | Active comparator | Device: Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS:Standard maintenance rTMS involves a course of rTMS with once-weekly sessions for 6 months. |
| sham maintenance rTMS | Placebo comparator | Device: Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMSSomatosensory-matched placebo rTMS is delivered according to either standard or clustered maintenance schedules over a six-month period (50/50% allotment). Patient's maintenance protocol parameters will otherwise mirror those used during their acute treatment with identical cortical targets, stimulation intensity, frequency, and duration. Sham TMS-EEG will be conducted by rotating the coil 90 degrees while maintaining contact with the scalp. This standard practice prevents current induction while replicating the auditory click associated with TMS, ensuring comparable EEG recordings |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- They met criteria for a DSM-5 diagnosis of a Major Depressive Episode (MDE) during the index episode of depression for which they have received an acute rTMS treatment course.
- Meet criteria for either response or remission from their initial depressive illness. The MINI assessment timeline will be adjusted to allow scoring of illness symptoms prior to rTMS response. Response to acute course of treatment is defined as either a MADRS score of <10, or a MADRS score of 10-19, plus evidence of having met response criteria on either the MADRS or another structured depression rating scale. The response is defined as a >50% reduction in the total score from the start to the end of treatment.
- Their initial rTMS treatment course must have consisted of at least 15 rTMS treatment sessions.
- People between the ages of 18 and 80 at the time of screening. A written statement from the referring physician will be required to confirm that the participant demonstrates the capacity to consent.
- Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during TMS-EEG assessments and iTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
Key exclusion criteria (2 listed)
- 1. Pregnancy 2. History of or current psychotic disorder or depression with psychotic features 3. Severe borderline personality disorder based on clinical assessment. 4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder 5. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal 6. Clinically significant suicidal ideation with plan 7. Any history of ECT (greater than 8 sessions) without a clinical meaningful response in the current episode.
- 8. Recent (during the current depressive episode) or concurrent use of rapid-acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days 9. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma 10. Untreated or insufficiently treated endocrine disorder. 11. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) 12. Treatment with an investigational drug or other intervention within the study period 13. The patient experiences a relapse between baseline and screening, defined as a moderate depression (MADRS >=20) and a 25% increase from screening to baseline 14. Require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any anticonvulsant (with the exception of Gabapentin, pregabalin, and lamotrigine).
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 |
|---|---|---|
| Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS:In this approach, patients who were treated with rTMS five days per week during their acute episode receive less frequent treatments during a taper period (for example treatment three days per week followed by two sessions per week) with a gradual transition into a maintenance schedule. For example, the maintenance schedule might begin with a single weekly session for one or two months and then the intensity is reduced to one session every two weeks (and possibly then one session every three or four weeks). | Device | Standard maintenance rTMS: |
| Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:Clustered maintenance rTMS typically involves around 4 TMS sessions applied over 2 days, at 1-month intervals. Our team initially developed this approach based upon preclinical TMS studies (for example (Maeda et al. 2000)) suggesting that rTMS treatment effects may accumulate when applied over multiple sessions in a shorter period of time (Maeda et al. 2000). | Device | Clustered maintenance rTMS |
| Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMSSham treatment will be administered as either standard or clustered maintenance rTMS for 6 months period using a sham coil. The intervention target will be located via a Brainsight TMS Navigator (Brainsight, Montreal, Canada). For safety reasons, the individual TMS intensity will be limited to 130% of the individual resting motor threshold. | Device | sham maintenance rTMS |
Primary outcome
Aim: To evaluate the effects of two active rTMS maintenance treatments (i.e., standard and clustered) compared to sham maintenance rTMS on DLPFC-SGC connectivity.
Time frame: 6-months
Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- 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.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS: and Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS: in people with Major Depressive Disorder and Treatment Resistant Depression, run by University of California, San Diego at 3 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 8 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Australia. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Interventional Psychiatry (858-657-6152, iptrials@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aim: To evaluate the effects of two active rTMS maintenance treatments (i.e., standard and clustered) compared to sham maintenance rTMS on DLPFC-SGC connectivity. (time frame: 6-months). 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 29 Apr 2026.