Pharmacologic Augmentation of TMS for Depression With D-serine

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-01

Study Completion Date

2026-04-01

Brief Summary

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The goal of this study is to test whether combining D-serine with 30 treatments of a) iTBS and b) 18-Hz protocols will enhance clinical outcomes compared to rTMS with placebo (i.e., sugar pill). The investigators hypothesize that NMDA receptor activation via D-serine combined with repeated sessions of rTMS will produce greater clinical outcomes than iTBS with placebo and 18-Hz with placebo.

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Detailed Description

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Consent Process:

After referral from the clinician, subjects will be contacted either by phone, by email, or in person, advised of the opportunity to participate in this study, and informed about what the study will entail. Subjects will give their own consent and will be over the age of 18.

Study Procedures:

All procedures may be available to all participants. If the participant agrees to take part in this study, the participant will be asked to undergo the following procedures during the experimental visit.

Clinical Measurement Initiative (CMI) Data: As part of routine clinical care, patients receiving TMS at McLean Hospital complete computerized clinician administered and patient self-reported assessments of clinical symptoms on admission and at interim and discharge points in their care. The computerized assessments are part of McLean Hospitals Clinical Measurement Initiative (CMI), which uses Research Electronic Data Capture (REDCap) software and a McLean-developed reporting module to generate individual patient reports used in ongoing clinical care and patient outcomes monitoring. The CMI was implemented in the McLean TMS program in May 2010. The investigators plan to conduct data analyses examining changes in TMS patient self-report of symptoms on the following standardized, validated surveys: Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR) and Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 which will be self-administered at treatment #1, #9, #14, #19, #24, #29, and #34, as well as clinician-administered Clinical Global Impression-Severity (CGI-S) at the point of consultation.

Transcranial Magnetic Stimulation (TMS): TMS involves a procedure where parts of the participant's brain will be non-invasively (i.e. indirectly) stimulated by magnetic pulses. Repetitive TMS (rTMS) administered in the study does not differ from standard of care as practiced in the McLean Clinic. Therefore, all patients will receive standard of care treatment combined along with either placebo or d-serine, designed to enhance clinical benefits.

Visits:

All visits follow our normal clinical schedule:

Visit 1: Participants will first undergo a TMS consultation to determine eligibility to safely receive TMS and assess clinical appropriateness for TMS.

Visit 2-37: 30 sessions of rTMS sessions (10-20 minutes long) daily, Mondays through Fridays, excluding weekends and holidays.

Drugs to be used (dose, method, schedule of administration, dose modifications, toxicities), include:

D-serine, 80 mg/kg (max 7g), oral administration, will be advised to be taken 1-hour prior rTMS treatment day (Mon-Fri) for 6 weeks. Dosing is based on maximal plasticity at 80 mg/kg, and clinical dose-finding studies demonstrating that doses between 60 - 120 mg/kg were superior in clinical effectiveness to 30 mg/kg and were safe. The drug will stopped at the discretion of the study clinicians after evaluation and assessment of any signs of adverse effects or signs of clinical worsening.

Conditions

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Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The proposed study is a randomized controlled trial with two groups: 1) placebo + TMS and 2) DS + TMS.

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Subjects will be randomized into the placebo (n = 30) or D-serine group (n = 30) via a randomization list generated by the McLean Pharmacy to produce equal groups. The research pharmacist is the only one unblinded and will create the randomization table for the placebo and D-serine assignments. The study staff will then pick up the medications in a blinded state (e.g., bottles labeled "A" or "B"). Only at the end of the study will the pharmacy then reveal the drugs corresponding to the label. The placebo is sourced from the same pharmacy as D-serine and have been requested to be in identical capsules.

Subjects will not be randomized into their TMS group and will either receive iTBS using our Magventure TMS device or 18-Hz H1 TMS using our dTMS Brainsway device. Subjects will have their TMS protocol/treatment determined at the time of consultation according to clinical appropriateness as is the standard of care at the TMS clinic at McLean Hospital.

Study Groups

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Placebo

Placebo + TMS

Group Type PLACEBO_COMPARATOR

TMS

Intervention Type DEVICE

Subjects will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device plus placebo.

D-serine

D-serine + TMS

Group Type ACTIVE_COMPARATOR

D-serine + TMS

Intervention Type COMBINATION_PRODUCT

D-serine, 80 mg/kg, oral administration, will be advised to be taken 1-hour prior rTMS treatment day (Mon-Fri) for 6 weeks. Dosing is based on maximal plasticity at 80 mg/kg, and clinical dose-finding studies demonstrating that doses between 60 - 120 mg/kg were superior in clinical effectiveness to 30 mg/kg and were safe.

Subjects will not be randomized into their TMS group and will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device. Subjects will have their TMS protocol/treatment determined at the time of consultation according to clinical appropriateness as is the standard of care at the TMS clinic at McLean Hospital.

Interventions

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TMS

Subjects will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device plus placebo.

Intervention Type DEVICE

D-serine + TMS

D-serine, 80 mg/kg, oral administration, will be advised to be taken 1-hour prior rTMS treatment day (Mon-Fri) for 6 weeks. Dosing is based on maximal plasticity at 80 mg/kg, and clinical dose-finding studies demonstrating that doses between 60 - 120 mg/kg were superior in clinical effectiveness to 30 mg/kg and were safe.

Subjects will not be randomized into their TMS group and will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device. Subjects will have their TMS protocol/treatment determined at the time of consultation according to clinical appropriateness as is the standard of care at the TMS clinic at McLean Hospital.

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

* Clinical diagnosis of MDD
* English-speaking
* Adults aged 18-80
* Must be able to swallow capsules

Exclusion Criteria

* Containing any implanted metal or devices
* Current or previous seizure history
* Active substance use that may significantly alter the seizure threshold

Any further safety clearances, and outpatient consultation opinions that are necessitated based on the answers to the screening will be obtained prior to moving forward with the study, as an already established practice within the clinic practice. In addition, any relative contraindications will be further reviewed according to Rossi et al.'s most updated safety guidelines for TMS.

* Patients with pre-existing renal disease
* Known allergy to D-serine, or with
* Patients taking medications with known drug-drug interactions
* Children
* Pregnant or breast-feeding women

The investigators will not include children because prior safety and dosing studies excluded children. Although considered safe for TMS, the investigators will not include pregnant or breast-feeding women on the basis of unknown safety profile of exogenous D-serine for these patients.

Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No