An Early Phase 1 interventional study of TMS and NRX-101 in Major Depression, sponsored by Mclean Hospital. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-30.
Sponsored by Mclean Hospital · Early Phase 1, Interventional, and Treatment
In this pilot study, investigators aim to combine D-cycloserine, lurasidone, and single-day repeated intermittent Theta Burst Stimulation (iTBS) to preliminarily assess clinical improvement in an open-label cohort and monitor for adverse events over a 6-week follow-up period.
Current therapeutic approaches for depression are limited in efficacy and accessibility. For many patients, Transcranial Magnetic Stimulation (TMS) has provided relief from treatment-resistant depression; however, invetigators are still far from maximizing the benefits of TMS. Here, investigators combine state-of-the-art interventions proven in depression (D-cycloserine (DCS), lurasidone (LRD), rapid intermittent Theta Burst Stimulation (iTBS)) with the aim of inducing and capitalizing on brain plasticity to support the alleviation of depressive symptoms.
The rationale for pharmacologically augmenting TMS is that 100 mg/day DCS with repetitive TMS, as proposed here, has been demonstrated to enhance remission and response rates in patients with depression in two weeks, with no serious adverse events reported in this trial of 50 patients. Importantly, previous studies examining DCS efficacy as an adjunct to antidepressant regimens also found no adverse events and a trend-level improvement of depression severity, and another evaluating safety for treatment of TB in patients with and without depression found an overall decrease in depression severity over treatment course. Combining DCS with LRD (NRX-101) should enhance these effects because it will modulate activity of both NMDA and 5-HT7 receptors in a manner that should reduce depressive symptoms. Indeed, Phase 2 clinical trial data showed clinical superiority of NRX-101 over LRD only for treating bipolar disorder, with no serious adverse events in 22 completers.
For transparency, investigators note here that while depression is listed as a contraindication when DCS is used to treat tuberculosis, the label reflects risks associated with DCS doses approximately 20 times higher than those used for modulation of neuroplasticity. Higher doses of DCS produce opposite (antagonistic) effects of the NMDA receptor relative to lower doses (agonistic), and dose-dependent side effects such as depression present at the highest doses (Lexicomp). investigators plan to use small doses of DCS that, when paired with TMS, have been shown to reduced depressive symptoms with minimal side effects.
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 30 is below the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Mclean Hospital is the lead sponsor of 185 studies on the registry; 32 are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 12 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
20 sessions of active iTBS combined with a single dose of NRX-101
Device: TMS · Drug: NRX-101
Transcranial Magnetic Stimulation (TMS): TMS involves a procedure where a coil is placed on the scalp and magnetic energy enters the participant's brain in pulses. TMS does not alter consciousness or impose restrictions of any kind on a participant after a session. Single pulses of TMS are delivered to probe cortical excitability, as a surrogate of plasticity, before and after each treatment session. Excitability is measured with neurophysiology including electromyography (EMG). Repetitive TMS (rTMS) administered in the study is delivered in a pattern protocol called intermittent-theta burst stimulation (iTBS) which has been FDA-cleared for-and shown to be effective in-the treatment of depression. We aim to deliver up to 20 sessions per day but can adapt for patient or staff related scheduling challenges or tolerability
Also known as: Transcranial Magnetic Stimulation, iTBS
NRX-101 is a combination capsule of fixed dose d-cycloserine (175 mg) and lurasidone (8.25 mg)
Also known as: lurasidone and d-cycloserine
Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
Clinician-rated measure of depressive symptom severity. Higher scores indicate worse symptoms. The minimum is 0, maximum is 60.
Time frame: From day of treatment to six weeks after treatment
Hamilton Depression Rating Scale (HAM-D)
Clinician-rated measure of depressive symptom severity. Higher score indicate worse symptoms. The minimum is 0, the maximum is 52.
Time frame: From day of treatment to six weeks after treatment
Patient Health Questionnaire 9-item (PHQ-9)
self-rated measure of depression symptom severity. Higher scores indicate worse symptoms. The minimum is 0, and the maximum is 27.
Time frame: From day of treatment to six weeks after treatment
Plan to share: Yes — De-identified individual participant data will be shared through the National Institute of Mental Health Data Archive (NDA) in accordance with NIMH data sharing expectations. Data to be shared will include demographic information and clinical scale scores. Data will be submitted to the NDA following standard de-identification procedures and will be made available to qualified researchers through the NDA data access request process.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Analytic code
Time frame: Data will be submitted to the NDA within 1 year of primary study completion or upon publication of primary results, whichever comes first.
Access criteria: Data will be accessible to qualified researchers through the NIMH Data Archive data access request process.
Data sharing details ↗ · nda.nih.gov
Started Oct 2026 (actual). Primary completion is estimated for Dec 2026, 2 months after the start.
Of 48 non-industry phase 1 interventional studies under Depressive Disorder, Major, half reached primary completion within 43 months of starting (the median), counting those still running; a quarter within 16. This study's planned 2 months is below that.
Counting every sponsor, half of 88 studies reached it within 16 months; a quarter within 5 and three quarters within 45.
Start moved once since we started tracking on Sep 25, 2026: Sep 2026 → Oct 2026, on Oct 30, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Desethyloxybutynin