A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial

NCT07227103 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: NRX101-011
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

Major depressive disorder (MDD) is a significant public health problem and leading cause of worldwide disability. Treatment resistance is common in MDD, however, for these individuals, targeted noninvasive brain stimulation is an alternative. Repetitive transcranial magnetic stimulation (rTMS) and more recently, theta-burst stimulation (TBS), are the noninvasive brain stimulation modalities with the largest evidence base in MDD. Although efficacious, an unacceptable proportion of patients do not significantly improve, and several aspects of the TMS parameter space are under investigation to enhance clinical outcomes. DCS has been shown in a randomized trial of more than double the percent response and remission from traditional TMS. When a one day (ONE-D) TMS protocol was combined with DCS, the measured response rate was 87% at one week. This trial will compare response and remission at six weeks following neuronavigated robotic-enabled Transcranial Magnetic Stimulation + NRX-101 (D-cycloserine/lurasidone) vs. TMS+placebo.

Conditions

Treatment Resistant Depression; Treatment Resistant Depression (TRD)

Keywords

Depression; TRD; Transcranial Magnetic Stimulation; TMS; neuronavigation; cycloserine; D-cycloserine; NRX-101; NMDA

Outcome Measures

Primary Outcomes (2)

• MADRS Depression

  Montgomery Asberg Depression Rating Scale Total Score

  6 weeks

• CGI-SS Suicidality

  Clinical Global Impression Suicidality Scale

  6 weeks

Secondary Outcomes (6)

• EMOCARE Depression Thermometer

  6 weeks

• Percent Response on MADRS

  Six weeks

• Percent Remission from Depression on MADRS

  Six weeks

• Percent Remission from Suicidality on CGI-SS

  Six weeks

• Percent Improvement on EMOBOT

  Six weeks

Study Arms (3)

Transcranial Magnetic Stimulation plus NRX-101

EXPERIMENTAL

Participants are treated with ONE-D TMS plus NRX-101 175mg DCS/8.5mg Lurasidone once daily for five days

Device: Neuronavigated robotic-enabled TMS; Drug: NRX-101

Transcranial Magnetic Stimualtion

PLACEBO COMPARATOR

Participants are treated with ONE-D TMS plus placebo once daily for five days

Device: Neuronavigated robotic-enabled TMS; Drug: Oral Placebo

Sham TMS + NRX-101

EXPERIMENTAL

Participants will be treated with Sham TMS (i.e. a TMS coil that does not deliver effective energy to the brain) + NRX-101

Drug: NRX-101; Device: Sham TMS

Interventions

NRX-101 DRUG

D-cycloserine 175mg + Lurasidone 8.5mg

Sham TMS + NRX-101; Transcranial Magnetic Stimulation plus NRX-101

Oral Placebo DRUG

An oral placebo capsule visually identical to NRX-101

Transcranial Magnetic Stimualtion

Neuronavigated robotic-enabled TMS DEVICE

One Day TMS Protocol performed with the Zeta Surgical neuronavigated robotic-enabled system and the neurocare Apollo TMS Device 30 Theta burst pulses delivered as per protocol

Transcranial Magnetic Stimualtion; Transcranial Magnetic Stimulation plus NRX-101

Sham TMS DEVICE

An Apollo TMS device configured not to deliver effective energy to the brain

Sham TMS + NRX-101

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Myocardial infarction within 1 year of Screening.
• Diagnosis of angina pectoris.
• Prolonged QTc interval, as measured by Fridericia's correction formula (QTcF) ≥450 msec at Screening for males or ≥ 470 msec for females on 2 of 3 measurements at least 15 minutes apart prior to randomization on Day 1. 16. Diagnosis of chronic lung disease, excluding asthma. 17. Lifetime history of any of the following: neurologic conditions with structural cerebral damage, traumatic brain injury, multiple sclerosis, surgical procedures involving the brain or meninges, meningoencephalitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's Disease, Parkinson's Disease), mental retardation, stroke (ischemic or hemorrhagic), intracranial abscess, or any other disease/procedure/accident/intervention that, according to the clinician, is deemed associated with significant injury to, or malfunction of, the CNS. 18. History of epilepsy, personal history of seizure, family history of epilepsy or seizure in a first degree relative. 19. Diagnosis of parenchymal or leptomeningeal cancer.
• Diabetes mellitus fulfilling any of the following criteria:
• Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) \>8.0 percent at Screening.
• Admitted to the hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks.
• Not under physician care for diabetes mellitus.
• Not on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks prior to Screening. 180645 180645 Protocol NRX101-011\_ MIND1 V3.0 FINAL Pg. 8 NRX101-011 Protocol v3.0 9 Confidential

Sponsors & Collaborators

• NeuroRx, Inc.: lead
• Zeta Surgical, Inc.: collaborator
• neurocare group AG: collaborator
• HOPE Therapeutics, Inc.: collaborator

Study Sites (3)

Cohen and Associates

Sarasota, Florida, 34239, United States

Location

HOPE Accelerated Care

West Palm Beach, Florida, 33417, United States

Location

Harvard Mclean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Rebecca S Cohen, MD

CONTACT

9144049688; rcohen@hopetherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matched drug and placebo capsules
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: CEO, NeuroRx, Inc.
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 9, 2025
• First Posted: November 12, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: June 24, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: upon study inception
• Access Criteria: Protocol and ICF shared with all SAP and CSR upon signed confidentiality agreement

Locations

US (3)