Pharmacologic Augmentation of TMS for Depression With D-serine
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Mclean Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Patient Health Questionnaire 9 (PHQ-9)
Study Overview
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
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.
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Placebo
Placebo and TMS
Intervention: Placebo (Other)
Placebo
Placebo and TMS
Intervention: TMS (Device)
D-serine
D-serine and TMS
Intervention: TMS (Device)
D-serine
D-serine and TMS
Intervention: D-serine (Drug)
Outcomes
Primary Outcomes
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
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
Secondary Outcomes
- 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)
Investigators
Joshua C. Brown, MD, PhD
Assistant Professor
Mclean Hospital