Pharmacologic Augmentation of TMS for Depression With D-serine

NCT06876129 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 2024P001927
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Patient Health Questionnaire 9 (PHQ-9)

  The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 test evaluates several factors that revolve around the criteria used to professionally diagnose depression under the current DSM-5. The total score is calculated and can range from zero to 27, with 27 being the highest and indicative of the worst outcome/severity. * A score of 20 or higher indicates that severe major depression * Scoring between 15 and 19 suggests that there is possibly moderately severe major depression * Scoring between 10 and 14 means that you may have a moderate severity depression * A score between 5 and 9 reveals that mild symptoms of depression appear to exist

  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

Secondary Outcomes (2)

• Quick Inventory of Depressive Symptomatology (QIDS SR-16)

  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

• Generalized Anxiety Disorder-7 (GAD-7)

  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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo + TMS

Device: TMS

D-serine

ACTIVE COMPARATOR

D-serine + TMS

Combination Product: D-serine + TMS

Interventions

TMS DEVICE

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

Placebo

D-serine + TMS 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.

D-serine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

Related Publications (3)

• Kantrowitz JT, Malhotra AK, Cornblatt B, Silipo G, Balla A, Suckow RF, D'Souza C, Saksa J, Woods SW, Javitt DC. High dose D-serine in the treatment of schizophrenia. Schizophr Res. 2010 Aug;121(1-3):125-30. doi: 10.1016/j.schres.2010.05.012. Epub 2010 Jun 11.

  PMID: 20541910 BACKGROUND

• Sehatpour P, Kreither J, Lopez-Calderon J, Shastry AM, De Baun HM, Martinez A, Javitt DC. Network-level mechanisms underlying effects of transcranial direct current stimulation (tDCS) on visuomotor learning in schizophrenia. Transl Psychiatry. 2023 Nov 23;13(1):360. doi: 10.1038/s41398-023-02656-3.

  PMID: 37993420 BACKGROUND

• Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

  PMID: 33243615 BACKGROUND

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Kerry Ressler, MD, PhD

  Mclean Hospital

  STUDY DIRECTOR

Central Study Contacts

Joshua C Brown, MD, PhD

CONTACT

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

Julia Tom, BS, MSN

CONTACT

617-855-2678; jtom1@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

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

Study Record Dates

• First Submitted: August 12, 2024
• First Posted: March 14, 2025
• Study Start: April 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)