Recruiting
Early Phase 1

D-Cycloserine, Lurasidone, iTBS

Sponsor:

Mclean Hospital

Code:

NCT07785102

Conditions

Major Depression

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

TMS

NRX-101

Study Details

Brief summary:

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.

Conditions

Major Depression

Study ID

NCT07785102

Start date

Oct 1, 2026

Status verified date

Aug, 2026

Completion date

Mar 31, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Male or Female adults (+18 years old)
  • from any ethnic or racial background
  • with moderate to severe depression, as indicated by scores of: ≥ 20 on the MADRS; AND ≥ 10 on PHQ-9.

Exclusion Criteria:

  • History of manic or hypomanic symptoms;
  • lifetime DSM-5 psychotic spectrum disorder or current clinically significant psychotic symptoms;
  • active alcohol or substance use disorder that, in the opinion of a study physician/PI, is of sufficient severity to impede engagement in treatment or is associated with significant risk of medical withdrawal;
  • anorexia nervosa or eating disorder not otherwise specified that, in the opinion of a study physician/PI, is of sufficient severity to be associated with significant medical risks;
  • current suicide risk sufficient to require immediate hospitalization (C-SSRS 4 or above)
  • history of traumatic brain injury (TBI) that, in the opinion of a study physician/PI, would significantly increase risk of seizure;
  • any other significant neurological disorder likely to increase risk of seizure, in the opinion of a study physician/PI;
  • diagnosed neurodevelopmental disorder (e.g., autism, Down syndrome; Ehlers-Danlos Syndrome);
  • current diagnosis of delirium or greater than mild dementia;
  • cognitive disorder secondary to a general medical condition suggesting probable TBI or intellectual impairment;
  • Pregnant and breastfeeding women are not eligible to participate in this study excluded in line with prior work using DCS and TMS (Rossi et al., 2021). To confirm eligibility, all female participants of childbearing potential will be required to undergo a urine pregnancy test prior to enrollment. Additionally, if at any point during the study the participant or the researcher suspects that the participant may have become pregnant, a urine pregnancy test will be administered to ensure continued eligibility;
  • Participants with contraindications to TMS (e.g., metal in head or neck area), or at increased risk for adverse events (e.g., seizure history or markedly heightened risk factors for seizures, serious medical problems, implanted devices) will be excluded;
  • Participants with a known allergy to DCS or LRD will be excluded;
  • fMRI contraindications follow those of TMS and individuals unable to safely receive either will be excluded;
  • No healthy volunteers will be recruited;
  • No patients with involuntary hospitalization status will be recruited.

Study Design

Enrollment

30 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Open-label TMS + NRX-101

20 sessions of active iTBS combined with a single dose of NRX-101

Interventions

TMS

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

NRX-101

NRX-101 is a combination capsule of fixed dose d-cycloserine (175 mg) and lurasidone (8.25 mg)

Primary outcome measure

  • Change in Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: From day of treatment to six weeks after treatment ]

Central Contacts and Locations

Central contacts

Prem Ganesh, MS

617-855-2153pganesh@mgb.org

Dennis W Guevara

617-855-2340dguevara@mclean.harvard.edu

Locations

McLean Hospital

Recruiting

Belmont, Massachusetts, United States, 02478

Contacts

Dennis W Guevara

617-855-2340dguevara@mclean.harvard.edu

Prem Ganesh, MS

617-855-2153pganesh@mgb.org

More Information

Sponsor

Mclean Hospital

Last update posted

Oct 30, 2026

Last verified

Aug, 2026

Keywords

  • Transcranial Magnetic Stimulation
  • NRX101
  • Depression
  • Pharmacologic Augmentation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-31. This information was provided to ClinicalTrials.gov by Mclean Hospital on 2026-10-30. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.