RecruitingPhase 1NCT06876129

Pharmacologic Augmentation of TMS for Depression With D-serine

Sponsor

Mclean Hospital

Enrollment

60 participants

Start Date

Apr 1, 2025

Study Type

INTERVENTIONAL

Conditions

Depression

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.

Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria4

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

Exclusion Criteria10

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.

Interventions

DEVICETMS

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

COMBINATION_PRODUCTD-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.