NRX-101 + TMS for Treatment Resistant Depression

(DCS_TMS Trial)

Overseen By Rebecca S Cohen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NeuroRx, Inc.

Must be taking: SSRIs

Must not be taking: Oxcarbazepine, Carbamazepine

Disqualifiers: Substance use disorder, Schizophrenia, Eating disorders, Dementia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to help individuals with treatment-resistant depression. It tests whether combining Transcranial Magnetic Stimulation (TMS), a noninvasive brain stimulation technique, with the medication NRX-101 improves symptoms more than TMS with a placebo. Those who have struggled with depression despite trying at least two different antidepressants may be suitable for this study. Participants will receive either TMS with NRX-101 or TMS with a placebo, and the trial aims to determine which combination is more effective over six weeks. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it allows stable use of certain medications like benzodiazepines and hypnotics if they have been stable for at least 4 weeks before screening. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of NRX-101, which includes D-cycloserine (DCS) and lurasidone, with Transcranial Magnetic Stimulation (TMS) is generally well-tolerated. Studies have found that NRX-101 works better with TMS than lurasidone alone, especially for treating depression symptoms.

DCS helps the brain form new connections, potentially enhancing the effects of TMS for individuals with treatment-resistant depression. In terms of safety, no strong evidence indicates serious side effects when DCS is used with TMS.

Lurasidone, a component of NRX-101, has FDA approval for other mental health conditions, indicating general safety. Overall, current research and past studies suggest that this combination is safe, with few reported side effects. It is important to consult a healthcare provider about any concerns before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NRX-101 combined with Transcranial Magnetic Stimulation (TMS) for treatment-resistant depression because it offers a unique approach compared to traditional antidepressants like SSRIs or SNRIs. Unlike standard treatments, which typically rely on altering serotonin or norepinephrine levels over weeks, NRX-101 combines D-cycloserine, a compound that affects glutamate pathways, with lurasidone, an antipsychotic. This combination is believed to work more rapidly and directly on different neurochemical pathways associated with mood regulation. The addition of TMS, a non-invasive brain stimulation technique, further enhances its potential by directly stimulating brain regions involved in mood control, which could lead to quicker and more effective relief for patients who haven't responded to other treatments.

What evidence suggests that this trial's treatments could be effective for treatment-resistant depression?

Research has shown that NRX-101, a combination of D-cycloserine and lurasidone, is more effective than lurasidone alone in maintaining improved depression symptoms. This combination aims to enhance the effects of standard depression treatments while minimizing side effects. In this trial, participants will receive either Transcranial Magnetic Stimulation (TMS) plus NRX-101 or TMS plus a placebo. One study found that when a brain stimulation method called ONE-D TMS was used with D-cycloserine, 87% of participants responded positively after one week. This suggests that using TMS with NRX-101 could improve treatment outcomes for individuals with depression that hasn't responded to other treatments. Although some studies have shown mixed results, the combination of ingredients in NRX-101 holds promise for addressing difficult cases of depression. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with major depressive disorder (MDD) who haven't improved after standard treatments. Participants will receive Transcranial Magnetic Stimulation (TMS), a noninvasive brain stimulation, and must be able to take the study medication or placebo.

Inclusion Criteria

A patient is eligible for inclusion in this study if all of the following criteria apply:

Able to understand and provide written and dated informed consent prior to Screening

Deemed likely to comply with the study protocol, including communication of adverse events (AEs) and other clinically important information, including adherence to the text messaging component of the trial

Exclusion Criteria

A patient is ineligible for inclusion in this study if any of the following criteria apply:

Current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to Screening

History of phencyclidine (PCP)/ketamine drug abuse, or failed use of ketamine for depression or suicidality

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Transcranial Magnetic Stimulation plus either NRX-101 or placebo once daily for five days

6 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NRX-101

Trial Overview The study tests if NRX-101, when combined with TMS, is more effective than a placebo in treating resistant depression. Patients are randomly assigned to either the NRX-101 group or a placebo group while receiving TMS therapy.

How Is the Trial Designed?

Group I: Transcranial Magnetic Stimulation plus NRX-101 Experimental Treatment 2 Interventions

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

Group II: Transcranial Magnetic Stimualtion Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

NeuroRx, Inc.

Lead Sponsor

Trials

14

Recruited

1,600+

AMPA Health, Inc.

Collaborator

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423711/

NRX-101 (D-cycloserine plus lurasidone) vs ... - PubMed Central The fixed-dose combination of DCS and lurasidone was significantly more effective than lurasidone alone in maintaining improvement in depression ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02974010

Sequential Therapy for the Treatment of Severe Bipolar ... Due to the synergistic effects, the proposed NRX-101 combination capsule is also expected to avoid or minimize the significant undesired adverse effects ...

3. psychiatrist.com psychiatrist.com/news/how-nrx-could-upend-the-fight-against-depression-and-suicide/

How NRx Could Upend the Fight Against Depression and ... The results showed that the combination of D-cycloserine and lurasidone appeared to be significantly more effective than lurasidone alone in ...

4. nrxpharma.com nrxpharma.com/wp-content/uploads/2022/08/STABIL-B-poster-as-presented.pdf

Sequential Treatment With IV Ketamine Followed by ... These studies support the use of sequential treatment with ketamine followed by combined DCS+Lurasidone (NRX-101) in the treatment of ASIB. ABSTRACT. Outcome ...

5. fiercebiotech.com fiercebiotech.com/biotech/despite-trial-miss-nrx-pushes-antidepressant-forward-phase-3-patients-bipolar-depression

NRx antidepressant fails to reduce depression severity NRx's oral antidepressant has failed to reach statistical significance reducing depression severity in a phase 2/3 trial.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07227103

Study Details | NCT07227103 | A Randomized, Double ... When the AMPA 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 ...

7. hdrx.com hdrx.com/d-cycloserine-transcranial-magnetic-stimulation-tms-depression-treatment-michigan/

D-Cycloserine & TMS: Neuroplasticity Support for ... D-Cycloserine with Transcranial Magnetic Stimulation TMS may accel neuroplasticity in treatment-resistant depression. Prescription RX only.

8. mghpsychnews.org mghpsychnews.org/d-cycloserine-and-lurasidone-nrx-101-bipolar-depression/

D-Cycloserine and Lurasidone (NRX-101) for Maintenance ... The combination of DCS and lurasidone was significantly more effective than lurasidone alone in maintaining improvements in depression and reducing suicidal ...

9. mdpi.com mdpi.com/2076-3425/15/2/161

Emerging Medications for Treatment-Resistant Depression Results: Fifty clinical trials for TRD, 20 for anhedonia, and 25 for suicide were identified. Glutamate system modulation was the mechanism currently with the ...