One Day of Ultra-Accelerated TMS With a Dose of NRX-101 for Major Depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open-label pilot explores whether a combination of D-cycloserine, lurasidone (as NRX-101), and a single-day rapid TMS (iTBS) session can improve depressive symptoms. Participants receive the intervention and are followed for six weeks to monitor efficacy and safety. The approach aims to enhance brain plasticity and antidepressant response by pharmacologic augmentation of TMS. Prior data suggest possible benefits with DCS and TMS, and NRX-101 has shown promise in mood disorders in earlier studies. This trial focuses on feasibility and preliminary signals of efficacy in an early-phase setting.

Why it matters

Who can join: the full rules

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.

Where it's running

• McLean Hospital
  Belmont, Massachusetts, United States Recruiting

Study contacts

• Principal investigator: Kerry Ressler, MD, PhD — Mclean Hospital
• Study coordinator: Prem Ganesh, MS
• Email: pganesh@mgb.org
• Phone: 617-855-2153

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.