Major DepressionEarly Phase 1SPARC-LINCT07785102
Single Day of Ultra-accelerated TMS With a Single Dose of NRX-101
A Early Phase 1 study testing TMS and NRX-101 in people with Major Depression, run by Mclean Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depression
- What is being tested?
- TMS and NRX-101
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 31 Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
McLean Hospital
Belmont, Massachusetts, 02478
Dennis W Guevara, 617-855-2340, dguevara@mclean.harvard.edu
Prem Ganesh, MS, 617-855-2153, pganesh@mgb.org
About this study
Official title: SPARC-LI: Synaptic Plasticity Augmented Rapid Circuit Stimulation
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.
Read the detailed description
Current therapeutic approaches for depression are limited in efficacy and accessibility. For many patients, Transcranial Magnetic Stimulation (TMS) has provided relief from treatment-resistant depression; however, invetigators are still far from maximizing the benefits of TMS. Here, investigators combine state-of-the-art interventions proven in depression (D-cycloserine (DCS), lurasidone (LRD), rapid intermittent Theta Burst Stimulation (iTBS)) with the aim of inducing and capitalizing on brain plasticity to support the alleviation of depressive symptoms.
The rationale for pharmacologically augmenting TMS is that 100 mg/day DCS with repetitive TMS, as proposed here, has been demonstrated to enhance remission and response rates in patients with depression in two weeks, with no serious adverse events reported in this trial of 50 patients. Importantly, previous studies examining DCS efficacy as an adjunct to antidepressant regimens also found no adverse events and a trend-level improvement of depression severity, and another evaluating safety for treatment of TB in patients with and without depression found an overall decrease in depression severity over treatment course. Combining DCS with LRD (NRX-101) should enhance these effects because it will modulate activity of both NMDA and 5-HT7 receptors in a manner that should reduce depressive symptoms. Indeed, Phase 2 clinical trial data showed clinical superiority of NRX-101 over LRD only for treating bipolar disorder, with no serious adverse events in 22 completers.
For transparency, investigators note here that while depression is listed as a contraindication when DCS is used to treat tuberculosis, the label reflects risks associated with DCS doses approximately 20 times higher than those used for modulation of neuroplasticity. Higher doses of DCS produce opposite (antagonistic) effects of the NMDA receptor relative to lower doses (agonistic), and dose-dependent side effects such as depression present at the highest doses (Lexicomp). investigators plan to use small doses of DCS that, when paired with TMS, have been shown to reduced depressive symptoms with minimal side effects.
- Conditions
- Major Depression
- Being tested
- TMS, NRX-101
- Keywords
- Transcranial Magnetic Stimulation, NRX101, Depression, Pharmacologic Augmentation
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
Also called Transcranial Magnetic Stimulation, iTBS
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-101Drug
Also called lurasidone and d-cycloserine
NRX-101 is a combination capsule of fixed dose d-cycloserine (175 mg) and lurasidone (8.25 mg)
| Study group | Role | What they receive |
|---|---|---|
| Open-label TMS + NRX-101 | Experimental | 20 sessions of active iTBS combined with a single dose of NRX-101 Receives: Device: TMS; Drug: NRX-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From day of treatment to six weeks after treatment
Secondary outcomes (2)
Hamilton Depression Rating Scale (HAM-D)
Clinician-rated measure of depressive symptom severity. Higher score indicate worse symptoms. The minimum is 0, the maximum is 52.
Measured: From day of treatment to six weeks after treatment
Patient Health Questionnaire 9-item (PHQ-9)
self-rated measure of depression symptom severity. Higher scores indicate worse symptoms. The minimum is 0, and the maximum is 27.
Measured: From day of treatment to six weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2026
- Study start1 Oct 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kerry Ressler, Mclean Hospital
- Investigators
- Kerry Ressler, MD, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07785102
- Sponsor's protocol ID
- 2026P001458
- Acronym
- SPARC-LI
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2026
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified individual participant data will be shared through the National Institute of Mental Health Data Archive (NDA) in accordance with NIMH data sharing expectations. Data to be shared will include demographic information and clinical scale scores. Data will be submitted to the NDA following standard de-identification procedures and will be made available to qualified researchers through the NDA data access request process.
Publications
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.
PubMed 26364274Nierenberg 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.
PubMed 37815563Heresco-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.
PubMed 16677714Cole 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.
PubMed 34711062
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SPARC-LI: Synaptic Plasticity Augmented Rapid Circuit Stimulation
- ClinicalTrials.gov ID
- NCT07785102
- Acronym / sponsor ID
- SPARC-LI / 2026P001458
- Conditions
- Major Depression
- Keywords
- Transcranial Magnetic Stimulation, NRX101, Depression, Pharmacologic Augmentation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- 1 Oct 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 25 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Current therapeutic approaches for depression are limited in efficacy and accessibility. For many patients, Transcranial Magnetic Stimulation (TMS) has provided relief from treatment-resistant depression; however, invetigators are still far from maximizing the benefits of TMS. Here, investigators combine state-of-the-art interventions proven in depression (D-cycloserine (DCS), lurasidone (LRD), rapid intermittent Theta Burst Stimulation (iTBS)) with the aim of inducing and capitalizing on brain plasticity to support the alleviation of depressive symptoms.
The rationale for pharmacologically augmenting TMS is that 100 mg/day DCS with repetitive TMS, as proposed here, has been demonstrated to enhance remission and response rates in patients with depression in two weeks, with no serious adverse events reported in this trial of 50 patients. Importantly, previous studies examining DCS efficacy as an adjunct to antidepressant regimens also found no adverse events and a trend-level improvement of depression severity, and another evaluating safety for treatment of TB in patients with and without depression found an overall decrease in depression severity over treatment course. Combining DCS with LRD (NRX-101) should enhance these effects because it will modulate activity of both NMDA and 5-HT7 receptors in a manner that should reduce depressive symptoms. Indeed, Phase 2 clinical trial data showed clinical superiority of NRX-101 over LRD only for treating bipolar disorder, with no serious adverse events in 22 completers.
For transparency, investigators note here that while depression is listed as a contraindication when DCS is used to treat tuberculosis, the label reflects risks associated with DCS doses approximately 20 times higher than those used for modulation of neuroplasticity. Higher doses of DCS produce opposite (antagonistic) effects of the NMDA receptor relative to lower doses (agonistic), and dose-dependent side effects such as depression present at the highest doses (Lexicomp). investigators plan to use small doses of DCS that, when paired with TMS, have been shown to reduced depressive symptoms with minimal side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Open-label TMS + NRX-101 | Experimental | Device: TMS, Drug: NRX-10120 sessions of active iTBS combined with a single dose of NRX-101 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMSAlso: Transcranial Magnetic Stimulation, iTBSTranscranial 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 | Device | Open-label TMS + NRX-101 |
| NRX-101Also: lurasidone and d-cycloserineNRX-101 is a combination capsule of fixed dose d-cycloserine (175 mg) and lurasidone (8.25 mg) | Drug | Open-label TMS + NRX-101 |
Primary outcome
Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: From day of treatment to six weeks after treatment
Clinician-rated measure of depressive symptom severity. Higher scores indicate worse symptoms. The minimum is 0, maximum is 60.
2 secondary outcomes
Hamilton Depression Rating Scale (HAM-D)
Time frame: From day of treatment to six weeks after treatment
Patient Health Questionnaire 9-item (PHQ-9)
Time frame: From day of treatment to six weeks after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Results publication: PubMed 26364274Schade 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.
- Results publication: PubMed 37815563Nierenberg 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.
- Results publication: PubMed 16677714Heresco-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.
- Results publication: PubMed 34711062Cole 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data will be shared through the National Institute of Mental Health Data Archive (NDA) in accordance with NIMH data sharing expectations. Data to be shared will include demographic information and clinical scale scores. Data will be submitted to the NDA following standard de-identification procedures and will be made available to qualified researchers through the NDA data access request process.
Related trials for Major Depression
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kerry Ressler, MD, PhD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing TMS and NRX-101 in people with Major Depression, run by Mclean Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Prem Ganesh, MS (617-855-2153, pganesh@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) (time frame: From day of treatment to six weeks after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07785102, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.