Depression
Conditions
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. 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.
Interventions
DEVICETMS
Subjects will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device plus placebo.
DRUGD-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.
OTHERPlacebo
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.
Sponsors
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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.
Intervention model description
The proposed study is a randomized controlled trial with two groups: 1) placebo + TMS and 2) DS + TMS.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Health Questionnaire 9 (PHQ-9) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | This scale is a self-report measure of depression. Questions in the QIDS - SR-116 correlate with the nine DSM-IV symptom criterion domains, including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), and Psychomotor agitation/retardation (Q 15 - 16). Severity of depression can be judged based on the total score as seen below of lowest to highest score values and their correlating severity. Higher scores indicating a worse outcome. 1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression |
| 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 | The Generalized Anxiety Disorder - 7 Item Scale (GAD-7) is a self-administered questionnaire designed for screening and measuring the severity of generalized anxiety disorder (GAD). The GAD-7 consists of seven items that respondents rate based on their experiences over the past two weeks, with each item scored from 0 (not at all) to 3 (nearly every day). The cumulative score, ranging from 0 to 21, indicates the severity of GAD symptoms, with higher scores corresponding to greater anxiety levels. This simplicity in administration and interpretation makes the GAD-7 a practical tool for healthcare providers to quickly assess anxiety levels and monitor changes over time. |
Countries
United States
Contacts
CONTACTJoshua C Brown, MD, PhD
CONTACTJulia Tom, BS, MSN
STUDY_DIRECTORKerry Ressler, MD, PhD
Mclean Hospital
Outcome results
None listed