[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100637968":3},{"organization":4,"armGroups":7,"interventions":31,"overallOfficials":68,"centralContacts":72,"locations":82,"responsibleParty":104,"collaborators":107,"id":111,"slug":112,"hasResults":113,"nctId":114,"briefTitle":115,"officialTitle":115,"acronym":76,"eligibilityCriteria":116,"healthyVolunteers":117,"sex":118,"minAge":119,"maxAge":76,"enrollmentInfo":120,"targetDuration":76,"studyType":123,"phases":124,"briefSummary":127,"conditions":128,"keywords":131,"overallStatus":135,"whyStopped":76,"lastUpdateSubmitDate":136,"lastUpdatePostDateStruct":137,"startDateStruct":140,"completionDateStruct":142,"leadSponsor":144,"locationsCount":145},{"fullName":5,"class":6},"Mclean Hospital","OTHER",[8,15,21,27],{"label":9,"type":10,"description":11,"interventionNames":12},"Sham iTBS + Placebo","SHAM_COMPARATOR","Placebo TMS and placebo drug",[13,14],"Device: Sham iTBS","Drug: Placebo",{"label":16,"type":17,"description":18,"interventionNames":19},"iTBS + Placebo","PLACEBO_COMPARATOR","Active TMS and placebo drug",[20,14],"Device: TMS",{"label":22,"type":23,"description":24,"interventionNames":25},"iTBS + D-cycloserine","EXPERIMENTAL","Active TMS and active medication",[20,26],"Drug: D-cycloserine",{"label":28,"type":23,"description":24,"interventionNames":29},"iTBS + dextromethorphan",[20,30],"Drug: Dextromethophan",[32,40,48,55,62],{"type":33,"name":34,"description":35,"armGroupLabels":36,"otherNames":37},"DEVICE","Sham iTBS","ham intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex using a sham coil identical in appearance to the active coil. No active magnetic stimulation is delivered. Used to control for the sensory experience of TMS.",[9],[38,39],"Transcranial magnetic stimulation","sham",{"type":33,"name":41,"description":42,"armGroupLabels":43,"otherNames":44},"TMS","Active intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex combined with oral placebo. iTBS consists of 50 Hz triplets delivered in 2-second bursts at 5 Hz, totaling 600 pulses per session over approximately 3 minutes, delivered using a figure-of-8 coil with real-time neuronavigation at an intensity set relative to each participant's resting motor threshold.",[22,16,28],[45,46,47],"transcranial magnetic stimulation","iTBS","intermittent theta-burst stimulation",{"type":49,"name":50,"description":51,"armGroupLabels":52,"otherNames":53},"DRUG","D-cycloserine","D-cycloserine at 100 mg acts as a partial agonist at the glycine co-agonist site of the NMDA receptor, facilitating NMDAR-mediated synaptic transmission. It is administered orally approximately 2 hours before iTBS to coincide with near-peak plasma concentration. Compounded as 100 mg capsules.",[22],[54],"DCS",{"type":49,"name":56,"description":57,"armGroupLabels":58,"otherNames":59},"Dextromethophan","Dextromethorphan at 150 mg acts as an NMDA receptor antagonist, blocking NMDAR-mediated synaptic transmission at brain concentrations consistent with in vitro receptor blockade. Administered orally approximately 2 hours before iTBS.",[28],[60,61],"DMO","DXM",{"type":49,"name":63,"description":64,"armGroupLabels":65,"otherNames":66},"Placebo","Microcrystalline cellulose capsule identical to the drug capsules, administered 2 hours prior to iTBS treatment.",[9,16],[67],"PBO",[69],{"name":70,"affiliation":5,"role":71},"Joshua C Brown, MD, PhD","PRINCIPAL_INVESTIGATOR",[73,78],{"name":70,"role":74,"phone":75,"phoneExt":76,"email":77},"CONTACT","617-855-2944",null,"jbrown@mclean.harvard.edu",{"name":79,"role":74,"phone":80,"phoneExt":76,"email":81},"Prem Ganesh, MS","617-855-2153","pganesh@mgb.org",[83],{"facility":84,"status":76,"city":85,"state":86,"zip":87,"country":88,"countryCode":89,"cosmosGeoPoint":90,"geoPoint":95,"contacts":96},"McLean Hospital","Belmont","Massachusetts","02478","United States","US",{"type":91,"coordinates":92},"Point",[93,94],-71.17867,42.39593,{"lat":94,"lon":93},[97,101,103],{"name":98,"role":74,"phone":99,"phoneExt":76,"email":100},"Dennis W Guevara","617-855-2340","dguevara@mclean.harvard.edu",{"name":79,"role":74,"phone":102,"phoneExt":76,"email":81},"617-855-2677",{"name":70,"role":71,"phone":76,"phoneExt":76,"email":76},{"type":71,"investigatorFullName":105,"investigatorTitle":106,"investigatorAffiliation":5,"oldNameTitle":76,"oldOrganization":76},"Joshua C. Brown, MD, PhD","Director, TMS Research",[108],{"name":109,"class":110},"National Institute of Mental Health (NIMH)","NIH","100637968","phase-1-synaptic-mechanisms-of-intermittent-theta-burst-stimulation-for-major-depressive-disorder-100637968",false,"NCT07593222","Synaptic Mechanisms of Intermittent Theta Burst Stimulation for Major Depressive Disorder","Inclusion Criteria:\n\n* Can safely receive TMS and study drugs\n* Stable medication regimen for one month prior to study participation, and for the duration of the study\n* Not currently receiving TMS, ECT, or ketamine\n* No active safety concerns related to suicidality\n\nExclusion Criteria:\n\n* History of seizures or epilepsy\n* History of intracranial pathology or lesions from any etiology\n* History of traumatic brain injury including prolonged loss of consciousness more than 15 min\n* Signs of increased intracranial pressure\n* Any major neurological conditions (ex: recent stroke, tumor, neurodegenerative disorders, etc.)\n* Major medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)\n* Severe migraines that may result in treatment intolerance.\n* Inability to tolerate MRI.\n* Pregnancy\n* Known allergic reaction to d-cycloserine or dextromenthorphan",true,"ALL","18 Years",{"count":121,"type":122},100,"ESTIMATED","INTERVENTIONAL",[125,126],"PHASE1","PHASE2","Many people with depression do not get better with standard treatments like medications or talk therapy. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation treatment that uses magnetic pulses to stimulate areas of the brain involved in depression. One form of TMS called intermittent theta burst stimulation (iTBS) is FDA-cleared for depression and takes only 3 minutes to deliver. However, about one-third of patients do not respond to iTBS, and another one-third do not reach full remission. Improving iTBS requires a better understanding of how it works in the brain.\n\niTBS is thought to work by strengthening connections between brain cells, a process called synaptic plasticity. This process depends on a type of brain receptor called the NMDA receptor. Most of what researchers know about how iTBS affects these connections comes from studies of healthy people. It is not known whether iTBS works the same way in the prefrontal cortex - the brain region targeted during depression treatment - or in people who actually have depression.\n\nThis study has two phases.\n\nIn Phase 1, both healthy volunteers and people with depression will complete 4 research visits to test how iTBS changes brain activity in the prefrontal cortex and whether medications that increase or decrease NMDA receptor activity change those effects. Each visit involves active or sham (inactive) iTBS combined with one of three study medications: a placebo (inactive pill), d-cycloserine (a medication that increases NMDA receptor activity), or dextromethorphan (a medication that decreases NMDA receptor activity). Brain activity is measured before and after each TMS session using electroencephalography (EEG), a painless test that records electrical signals from the scalp through a cap placed on the head. All participants also complete a brain MRI before beginning study visits for targeting purposes.\n\nIn Phase 2, participants with depression will be offered a standard clinical course of 30 daily iTBS sessions (Monday through Friday over 6 weeks). Each session is combined with one blinded study medication (placebo, d-cycloserine, or dextromethorphan) taken daily. Brain activity measurements and standard depression and anxiety questionnaires are collected weekly throughout this phase to track how the brain changes over the course of treatment and whether those changes relate to improvements in symptoms.\n\nTogether, the two phases of this study aim to identify the brain mechanism by which iTBS works in people with depression. This knowledge could lead to more effective TMS treatments for people who have not responded to medications or other therapies.",[129,130],"Major Depression","Healthy Participants",[41,132,133,45,134],"depression","EEG","pharmacologic augmentation","NOT_YET_RECRUITING","2026-05-13",{"date":138,"type":139},"2026-05-18","ACTUAL",{"date":141,"type":122},"2026-07-01",{"date":143,"type":122},"2031-06-30",{"name":5,"class":6},1]