Pharmacologic Augmentation of TMS for Depression With D-serine
ConditionDepression
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorMclean Hospital
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Clinical diagnosis of MDD
English-speaking
Adults aged 18-80
Must be able to swallow capsules
Disqualifiers
Containing any implanted metal or devices
Current or previous seizure history
Active substance use that may significantly alter the seizure threshold
Patients with pre-existing renal disease
Trial design
Design model
Parallel
Treatments tested in this trial
TMS
DeviceSubjects will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device plus placebo.
D-serine
DrugD-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.
Placebo
Other interventionThe 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: PlaceboPlacebo comparator 2 interventions
Group B: D-serineActive comparator 2 interventions
Trial outcomes
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
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 weekSecondary outcomes
1
Quick Inventory of Depressive Symptomatology (QIDS SR-16)
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
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 week2
Generalized Anxiety Disorder-7 (GAD-7)
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.
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 weekSponsors and contacts
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Source ClinicalTrials.gov