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Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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).

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Clustered maintenance rTMS 		Clustered maintenance treatment involves administering four sessions of rTMS over a two-day span, conducted once per month for six months.
  • 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).
Active Comparator
Standard maintenance rTMS: 		Standard maintenance rTMS involves a course of rTMS with once-weekly sessions for 6 months.
  • Device: 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).
Placebo Comparator
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
  • 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.

Recruiting Locations

More Details

Status
Recruiting
Sponsor
University of California, San Diego

Study Contact

Interventional Psychiatry
858-657-6152
iptrials@health.ucsd.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.

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