Recruiting
Phase 1

D-Serine & rTMS

Sponsor:

Mclean Hospital

Code:

NCT06876129

Conditions

Depression

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

TMS

D-serine

Placebo

Study Details

Brief 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.

Conditions

Depression

Study ID

NCT06876129

Start date

Apr 1, 2025

Status verified date

Apr, 2026

Completion date

Apr 1, 2027

Anticipated

Primary completion date

Dec 26, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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

Relative contraindications/possible 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.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Placebo

Placebo and TMS

active comparator: D-serine

D-serine and TMS

Interventions

TMS

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, 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.

Placebo

The placebo is an inactive substance (e.g., lactose or cellulose) packaged to be identical in appearance, taste, and smell to the active study drug. Oral administration, will be advised to be taken 1-hour prior rTMS treatment day (Mon-Fri) for 6 weeks.

Primary outcome measure

  • Patient Health Questionnaire 9 (PHQ-9) [ Time Frame: Through TMS treatment course, average of 6-8 weeks; taken at treatment #1, #9, #14, #19, #24, #29, and #34, an average of once per week ]

Central Contacts and Locations

Central contacts

Joshua C Brown, MD, PhD

617-855-2944jbrown@mclean.harvard.edu

Julia Tom, BS, MSN

617-855-2678jtom1@mgb.org

Locations

McLean Hospital

Recruiting

Belmont, Massachusetts, United States, 02478

Contacts

Dennis Guevara

617-855-2340dguevara@mclean.harvard.edu

Joshua Brown, MD, PhD

617-855-2944jbrown@mclean.harvard.edu

More Information

Sponsor

Mclean Hospital

Last update posted

May 15, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mclean Hospital on 2026-05-15.