NCT06876129

Pharmacologic Augmentation of TMS for Depression With D-serine

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Mclean Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

• Depression

Interventions

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

Timeline

• Start date: 2025-04-01
• Primary completion: 2026-02-01
• Completion: 2026-04-01
• First posted: 2025-03-14
• Last updated: 2025-10-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study