Maintenance rTMS for Depression (Maitr-De)

NCT ID: NCT06938841

Last Updated: 2025-04-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-03-31

Brief 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. 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

Conditions

Major Depressive Disorder; Treatment Resistant Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Clustered maintenance rTMS

Clustered maintenance treatment involves administering four sessions of rTMS over a two-day span, conducted once per month for six months.

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:

Intervention Type: 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).

Standard maintenance rTMS:

Standard maintenance rTMS involves a course of rTMS with once-weekly sessions for 6 months.

Group Type: ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS:

Intervention Type: 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).

sham maintenance rTMS

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

Group Type: PLACEBO_COMPARATOR

Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMS

Intervention Type: DEVICE

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.

Interventions

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).

Intervention Type: DEVICE

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).

Intervention Type: DEVICE

Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMS

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 1. 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.

2. 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 <7, or a MADRS score of 7-19, 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.

3. Their initial rTMS treatment course must have consisted of at least 15 rTMS treatment sessions.

4. 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.

5. 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.

6. In good general health, as evidenced by medical history. 7. Agreement to adhere to Lifestyle Considerations throughout study duration. 8. 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

Exclusion Criteria

• 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. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.

14. Require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any anticonvulsant (with the exception of Gabapentin).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Zafiris Daskalakis

MD, PhD.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of California, San Diego

San Diego, California, United States

Site Status: RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status: RECRUITING

Australian National University

Canberra, Australian Capital Territory, Australia

Site Status: RECRUITING

Countries

United States; Australia

Central Contacts

Interventional Psychiatry

Role: CONTACT

iptrials@health.ucsd.edu

858-657-6152

Facility Contacts

Bianca Bacio

Role: primary

bbacio@health.ucsd.edu

858-657-6152

Connor Liston

Role: primary

Shona Brinley

Role: primary

shona.brinley@anu.edu.au

Paul B Fitzgerald, MBBS,MPM, PhD.

Role: backup

Other Identifiers

811708

Identifier Type: -

Identifier Source: org_study_id