Pharmacologic Augmentation of TMS for Depression With D-serine

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Patient Health Questionnaire 9 (PHQ-9) [Срок оценки: 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]

Вторичные конечные точки (2)

• Quick Inventory of Depressive Symptomatology (QIDS SR-16) [Срок оценки: 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) [Срок оценки: 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]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• McLean Hospital — Belmont

Публикации

• 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
• 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
• 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, Wasse PMID 33243615

Идентификаторы

NCT: NCT06876129 · 2024P001927

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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