Single Day of Ultra-accelerated TMS With a Single Dose of NRX-101

NCT07785102 | Not Yet Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 2026P001458
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Keywords

Transcranial Magnetic Stimulation; NRX101; Depression; Pharmacologic Augmentation

Outcome Measures

Primary Outcomes (1)

• 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.

  From day of treatment to six weeks after treatment

Secondary Outcomes (2)

• Hamilton Depression Rating Scale (HAM-D)

  From day of treatment to six weeks after treatment

• Patient Health Questionnaire 9-item (PHQ-9)

  From day of treatment to six weeks after treatment

Study Arms (1)

Open-label TMS + NRX-101

EXPERIMENTAL

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

Device: TMS; Drug: NRX-101

Interventions

TMS DEVICE

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

Open-label TMS + NRX-101

NRX-101 DRUG

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

Open-label TMS + NRX-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (4)

• Schade S, Paulus W. D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review. Int J Neuropsychopharmacol. 2016 Apr 20;19(4):pyv102. doi: 10.1093/ijnp/pyv102. Print 2016 Apr.

  PMID: 26364274 RESULT

• Nierenberg AA, Agustini B, Kohler-Forsberg O, Cusin C, Katz D, Sylvia LG, Peters A, Berk M. Diagnosis and Treatment of Bipolar Disorder: A Review. JAMA. 2023 Oct 10;330(14):1370-1380. doi: 10.1001/jama.2023.18588.

  PMID: 37815563 RESULT

• Heresco-Levy U, Javitt DC, Gelfin Y, Gorelik E, Bar M, Blanaru M, Kremer I. Controlled trial of D-cycloserine adjuvant therapy for treatment-resistant major depressive disorder. J Affect Disord. 2006 Jul;93(1-3):239-43. doi: 10.1016/j.jad.2006.03.004. Epub 2006 May 4.

  PMID: 16677714 RESULT

• Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.

  PMID: 34711062 RESULT

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Transcranial Magnetic Stimulation; Lurasidone Hydrochloride; Cycloserine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Isoxazoles; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Kerry Ressler, MD, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prem Ganesh, MS

CONTACT

617-855-2153; pganesh@mgb.org

Dennis W Guevara

CONTACT

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Scientific Officer

Model Details: This is an open-label pilot study of n = 30, where everyone receives a single day of ultra-accelerated TMS (uaTMS) with a single dose of NRX-101.

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 25, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: September 22, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (1)