Major Depressive DisorderPhase 2/3SAINT®SCNCT03693105
The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition
A Phase 2/3 study testing Active SAINT Stimulation in people with Major Depressive Disorder and Major Depressive Episode, run by Magnus Medical at 4 sites in United States.
Trial summary
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Major Depressive Disorder, Major Depressive Episode, Suicidal Ideation
- What is being tested?
- Active SAINT Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Jun 2024to 6 Mar 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults of all genders between the ages of 18 and 75 years at the time of screening.
- Able to read, understand, and provide written, dated informed consent prior to screening.
- Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS treatments. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- Currently diagnosed with either Major Depressive Disorder (MDD) and meets criteria for a current Major Depressive Episode (MDE) according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM).
- Endorses clinically significant explicit suicidal cognitions (score ≥ 9 on the M-SSI and score ≥ 6 on the BSS self-report) at screening.
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- MADRS score of >/=20 at screening (visit 1).
- rTMS/iTBS naive.
- Access to ongoing psychiatric care before and after completion of the study.
- Access to clinical rTMS after hospital discharge.
- In good general health, as evidenced by medical history.
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
- Agreement to adhere to Lifestyle considerations:
- Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9).
- Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 3 hours before the start of each dosing session until after the final TMS session.
- Abstain from alcohol for 24 hours before the start of each dosing session until after collection of the final MRI.
- Participants who use tobacco products will be instructed that use of cigarettes will not be allowed during the trial.
Who cannot join
- Females who are pregnant or planning to become pregnant during the course of the study or any female that is breastfeeding
- The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia in which in the Investigator's opinion is predominant to MDD
- Depressed mood/dysphoria as a result of an illness other than MDD (e.g. gender dysphoria)
- Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation)
- Current mania or psychosis
- Bipolar Affective Disorder I and primary psychotic disorders.
Show all 20Show fewer
- Autism Spectrum disorder or Intellectual Disability
- A diagnosis of obsessive-compulsive disorder (OCD)
- Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal.
- Urine screening test positive for illicit substances.
- Any history of ECT (greater than 8 sessions) without meeting responder criteria
- No recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT).
- History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma.
- Untreated or insufficiently treated endocrine disorder.
- Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
- Contraindications to MRI (ferromagnetic metal in their body).
- Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
- Treatment with another investigational drug or other intervention within the study period.
- Depth-adjusted SAINT® treatment dose > 65% maximum stimulator output (MSO)
- Any other condition deemed by the PI to interfere with the study or increase risk to the participant.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Texas, Austin
Austin, Texas, 78712
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
University of Iowa
Iowa City, Iowa, 52242
Weill Cornell Medicine
Manhattan, New York, 10021
About this study
Official title: A Multi-Site, Randomized, Double-Blind Trial Assessing The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days and measuring resting-state functional connectivity (RS FC) between the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN) at baseline and immediate-post visit. The relationship between changes in RS FC and changes in both Explicit and Implicit Suicidal Cognitions (ESC and ISC, respectively) will be determined. This study will also determine the relationship between changes in RS FC in neural networks underlying mediators of suicidal cognitions and changes in such mediators with active versus sham SAINT.
Read the detailed description
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT protocol (10 applications per day to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days) and measuring resting-state functional connectivity (RS FC) between the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN) at baseline and immediate-post visit. The relationship between changes in RS FC and changes in both Explicit and Implicit Suicidal Cognitions (ESC and ISC, respectively) will be determined. This study will also determine the relationship between changes in RS FC in neural networks underlying mediators of suicidal cognitions and changes in such mediators (i.e., depression, hopelessness, anhedonia) with active versus sham SAINT.
The mechanistic hypothesis is that active SAINT modulates RS FC underlying ESC (sgACC-DMN) and ISC (DLPFC-ACC) and that these changes in connectivity will correlate with reductions in ESC and ISC, respectively. MDD with current Major Depressive Episode will be defined according to DSM-5 criteria, and active SI will be defined by a baseline modified Scale for Suicide Ideation (M-SSI) score ≥ 9.
The primary objective is to determine if active versus sham SAINT aiTBS applied to the left dorsolateral prefrontal cortex (L-DLPFC)-subgenual anterior cingulate cortex (sgACC) is effective in modulating neural networks underlying explicit suicidal cognition (ESC) in psychiatric inpatients.
The secondary objective is to determine if active versus sham SAINT aiTBS applied to the L-DLPFC-sgACC is effective in modulating neural networks underlying implicit suicidal cognition (ISC) in psychiatric inpatients.
The tertiary objective is to determine if active versus sham SAINT aiTBS applied to the L-DLPFC-sgACC is effective in modulating neural networks underlying mediators of suicidal cognitions such as depression, hopelessness, and anhedonia.
The study will enroll approximately 100 participants and employ a two-arm design with 50 subjects per arm. The target population is adults of all genders and ethnicities who are between 18 and 75 years of age with a diagnosis of treatment-resistant MDD experiencing a current Major Depressive Episode, with active suicidal ideation, and who are otherwise in good general health. Participants must be without contraindications to Magnetic Resonance Imaging (MRI) or transcranial magnetic stimulation (TMS) and must be able to attend all study visits.
This study will deliver both active and sham SAINT via a MagPro X100 edition (MagVenture, Skovlunde, Denmark) TMS device equipped with a Cool-B65 A/P coil. The stimulation paradigm consists of 10 daily sessions (50 total over 5-days) of MNS with SAINT stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex). An operator entered code (derived from the study EDC) will instruct the device to deliver active or sham magnetic stimulation.
- Being tested
- Active SAINT Stimulation, Sham SAINT Stimulation
- Keywords
- Suicidality, Neuromodulation, Transcranial magnetic stimulation, Depression, Intermittent theta burst stimulation
- Medical subject headings
- Depressive Disorder, Major, Suicidal Ideation, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active SAINT StimulationDevice
Participants who are randomly assigned to this group will receive active SAINT targeted to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).
Stimulation will be delivered using the Magventure Magpro X100 TMS system with the Cool-B65 A/P coil.
Sham SAINT StimulationDevice
Participants who are randomly assigned to this group will receive sham stimulation targeted to the left DLPFC.
Sham stimulation will be delivered using the Magventure Magpro X100 TMS system with the Cool-B65 A/P coil.
| Study group | Role | What they receive |
|---|---|---|
| SAINT stimulation | Active comparator | Active SAINT stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) Receives: Device: Active SAINT Stimulation |
| Sham stimulation | Sham comparator | Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) Receives: Device: Sham SAINT Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the neural network underlying Explicit Suicidal Cognition (ESC) as measured by resting state functional connectivity changes in subgenual anterior cingulate (sgACC) and the default mode network (DMN).
We will assess resting state functional connectivity between sgACC and the DMN and within the DMN using magnetic resonance imaging.
Measured: At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Secondary outcomes (1)
Change in the neural network underlying Implicit Suicidal Cognition (ISC) as measured by resting state functional connectivity changes in dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC).
We will use resting state functional connectivity of DLPFC to the ACC using magnetic resonance imaging.
Measured: At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2018
- Study start30 Jun 2024
- Primary completion6 Mar 2025
- Study completion6 Mar 2025
Why it stopped: Funding discontinued.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will receive either active or sham stimulation to the DLPFC. Patients will be randomized to either condition with a 50:50 chance.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Magnus Medical
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Brandon Bentzley, MD, Study director, Magnus Medical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03693105
- Sponsor's protocol ID
- CLN-0105
- Other IDs
- R01MH125160
- Acronym
- SAINT®SC
- Status last verified
- Oct 2024
- First submitted
- 27 Sep 2018
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
PubMed 20439832George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
PubMed 8547583Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
PubMed 8684201Abdallah CG, Averill LA, Collins KA, Geha P, Schwartz J, Averill C, DeWilde KE, Wong E, Anticevic A, Tang CY, Iosifescu DV, Charney DS, Murrough JW. Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology. 2017 May;42(6):1210-1219. doi: 10.1038/npp.2016.186. Epub 2016 Sep 8.
PubMed 27604566Liston C, Chen AC, Zebley BD, Drysdale AT, Gordon R, Leuchter B, Voss HU, Casey BJ, Etkin A, Dubin MJ. Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry. 2014 Oct 1;76(7):517-26. doi: 10.1016/j.biopsych.2014.01.023. Epub 2014 Feb 5.
PubMed 24629537Green KL, Brown GK, Jager-Hyman S, Cha J, Steer RA, Beck AT. The Predictive Validity of the Beck Depression Inventory Suicide Item. J Clin Psychiatry. 2015 Dec;76(12):1683-6. doi: 10.4088/JCP.14m09391.
PubMed 26717528Ballard ED, Reed JL, Szczepanik J, Evans JW, Yarrington JS, Dickstein DP, Nock MK, Nugent AC, Zarate CA Jr. Functional Imaging of the Implicit Association of the Self With Life and Death. Suicide Life Threat Behav. 2019 Dec;49(6):1600-1608. doi: 10.1111/sltb.12543. Epub 2019 Feb 13.
PubMed 30761601Tello N, Harika-Germaneau G, Serra W, Jaafari N, Chatard A. Forecasting a Fatal Decision: Direct Replication of the Predictive Validity of the Suicide-Implicit Association Test. Psychol Sci. 2020 Jan;31(1):65-74. doi: 10.1177/0956797619893062. Epub 2019 Dec 11.
PubMed 31825760Light SN, Bieliauskas LA, Taylor SF. Measuring change in anhedonia using the "Happy Faces" task pre- to post-repetitive transcranial magnetic stimulation (rTMS) treatment to left dorsolateral prefrontal cortex in Major Depressive Disorder (MDD): relation to empathic happiness. Transl Psychiatry. 2019 Sep 3;9(1):217. doi: 10.1038/s41398-019-0549-8.
PubMed 31481688Baeken C, Duprat R, Wu GR, De Raedt R, van Heeringen K. Subgenual Anterior Cingulate-Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment? Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Oct;2(7):556-565. doi: 10.1016/j.bpsc.2017.01.001. Epub 2017 Jan 20.
PubMed 29560909Downar J, Geraci J, Salomons TV, Dunlop K, Wheeler S, McAndrews MP, Bakker N, Blumberger DM, Daskalakis ZJ, Kennedy SH, Flint AJ, Giacobbe P. Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression. Biol Psychiatry. 2014 Aug 1;76(3):176-85. doi: 10.1016/j.biopsych.2013.10.026. Epub 2013 Nov 28.
PubMed 24388670Duprat R, De Raedt R, Wu GR, Baeken C. Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity. Front Hum Neurosci. 2016 Jun 16;10:294. doi: 10.3389/fnhum.2016.00294. eCollection 2016.
PubMed 27378888Schmaal L, van Harmelen AL, Chatzi V, Lippard ETC, Toenders YJ, Averill LA, Mazure CM, Blumberg HP. Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies. Mol Psychiatry. 2020 Feb;25(2):408-427. doi: 10.1038/s41380-019-0587-x. Epub 2019 Dec 2.
PubMed 31787757Gartner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Boker H, Hattenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.
PubMed 30819549
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Site, Randomized, Double-Blind Trial Assessing The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition
- ClinicalTrials.gov ID
- NCT03693105
- Acronym / sponsor ID
- SAINT®SC / CLN-0105
- Keywords
- Suicidality, Neuromodulation, Transcranial magnetic stimulation, Depression, Intermittent theta burst stimulation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding discontinued.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Magnus MedicalIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 30 Jun 2024 (actual)
- Primary completion
- 6 Mar 2025 (actual)
- Study completion
- 6 Mar 2025 (actual)
- First posted
- 2 Oct 2018 (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.
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days and measuring resting-state functional connectivity (RS FC) between the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN) at baseline and immediate-post visit. The relationship between changes in RS FC and changes in both Explicit and Implicit Suicidal Cognitions (ESC and ISC, respectively) will be determined. This study will also determine the relationship between changes in RS FC in neural networks underlying mediators of suicidal cognitions and changes in such mediators with active versus sham SAINT.
Detailed description
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT protocol (10 applications per day to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days) and measuring resting-state functional connectivity (RS FC) between the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN) at baseline and immediate-post visit. The relationship between changes in RS FC and changes in both Explicit and Implicit Suicidal Cognitions (ESC and ISC, respectively) will be determined. This study will also determine the relationship between changes in RS FC in neural networks underlying mediators of suicidal cognitions and changes in such mediators (i.e., depression, hopelessness, anhedonia) with active versus sham SAINT.
The mechanistic hypothesis is that active SAINT modulates RS FC underlying ESC (sgACC-DMN) and ISC (DLPFC-ACC) and that these changes in connectivity will correlate with reductions in ESC and ISC, respectively. MDD with current Major Depressive Episode will be defined according to DSM-5 criteria, and active SI will be defined by a baseline modified Scale for Suicide Ideation (M-SSI) score ≥ 9.
The primary objective is to determine if active versus sham SAINT aiTBS applied to the left dorsolateral prefrontal cortex (L-DLPFC)-subgenual anterior cingulate cortex (sgACC) is effective in modulating neural networks underlying explicit suicidal cognition (ESC) in psychiatric inpatients.
The secondary objective is to determine if active versus sham SAINT aiTBS applied to the L-DLPFC-sgACC is effective in modulating neural networks underlying implicit suicidal cognition (ISC) in psychiatric inpatients.
The tertiary objective is to determine if active versus sham SAINT aiTBS applied to the L-DLPFC-sgACC is effective in modulating neural networks underlying mediators of suicidal cognitions such as depression, hopelessness, and anhedonia.
The study will enroll approximately 100 participants and employ a two-arm design with 50 subjects per arm. The target population is adults of all genders and ethnicities who are between 18 and 75 years of age with a diagnosis of treatment-resistant MDD experiencing a current Major Depressive Episode, with active suicidal ideation, and who are otherwise in good general health. Participants must be without contraindications to Magnetic Resonance Imaging (MRI) or transcranial magnetic stimulation (TMS) and must be able to attend all study visits.
This study will deliver both active and sham SAINT via a MagPro X100 edition (MagVenture, Skovlunde, Denmark) TMS device equipped with a Cool-B65 A/P coil. The stimulation paradigm consists of 10 daily sessions (50 total over 5-days) of MNS with SAINT stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex). An operator entered code (derived from the study EDC) will instruct the device to deliver active or sham magnetic stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will receive either active or sham stimulation to the DLPFC. Patients will be randomized to either condition with a 50:50 chance.
| Arm | Type | Receives |
|---|---|---|
| SAINT stimulation | Active comparator | Device: Active SAINT StimulationActive SAINT stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) |
| Sham stimulation | Sham comparator | Device: Sham SAINT StimulationSham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Adults of all genders between the ages of 18 and 75 years at the time of screening.
- Able to read, understand, and provide written, dated informed consent prior to screening.
- Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS treatments. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- Currently diagnosed with either Major Depressive Disorder (MDD) and meets criteria for a current Major Depressive Episode (MDE) according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM).
Key exclusion criteria (20 listed)
- Females who are pregnant or planning to become pregnant during the course of the study or any female that is breastfeeding
- The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia in which in the Investigator's opinion is predominant to MDD
- Depressed mood/dysphoria as a result of an illness other than MDD (e.g. gender dysphoria)
- Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation)
- Current mania or psychosis
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 |
|---|---|---|
| Active SAINT StimulationParticipants who are randomly assigned to this group will receive active SAINT targeted to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system with the Cool-B65 A/P coil. | Device | SAINT stimulation |
| Sham SAINT StimulationParticipants who are randomly assigned to this group will receive sham stimulation targeted to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system with the Cool-B65 A/P coil. | Device | Sham stimulation |
Primary outcome
Change in the neural network underlying Explicit Suicidal Cognition (ESC) as measured by resting state functional connectivity changes in subgenual anterior cingulate (sgACC) and the default mode network (DMN).
Time frame: At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
We will assess resting state functional connectivity between sgACC and the DMN and within the DMN using magnetic resonance imaging.
1 secondary outcome
Change in the neural network underlying Implicit Suicidal Cognition (ISC) as measured by resting state functional connectivity changes in dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC).
Time frame: At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Results and safety
The study was stopped early (reason given: Funding discontinued.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Background: PubMed 20439832George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
- Background: PubMed 8547583George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
- Background: PubMed 8684201Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
- Background: PubMed 27604566Abdallah CG, Averill LA, Collins KA, Geha P, Schwartz J, Averill C, DeWilde KE, Wong E, Anticevic A, Tang CY, Iosifescu DV, Charney DS, Murrough JW. Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology. 2017 May;42(6):1210-1219. doi: 10.1038/npp.2016.186. Epub 2016 Sep 8.
- Background: PubMed 24629537Liston C, Chen AC, Zebley BD, Drysdale AT, Gordon R, Leuchter B, Voss HU, Casey BJ, Etkin A, Dubin MJ. Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry. 2014 Oct 1;76(7):517-26. doi: 10.1016/j.biopsych.2014.01.023. Epub 2014 Feb 5.
- Background: PubMed 26717528Green KL, Brown GK, Jager-Hyman S, Cha J, Steer RA, Beck AT. The Predictive Validity of the Beck Depression Inventory Suicide Item. J Clin Psychiatry. 2015 Dec;76(12):1683-6. doi: 10.4088/JCP.14m09391.
- Background: PubMed 30761601Ballard ED, Reed JL, Szczepanik J, Evans JW, Yarrington JS, Dickstein DP, Nock MK, Nugent AC, Zarate CA Jr. Functional Imaging of the Implicit Association of the Self With Life and Death. Suicide Life Threat Behav. 2019 Dec;49(6):1600-1608. doi: 10.1111/sltb.12543. Epub 2019 Feb 13.
- Background: PubMed 31825760Tello N, Harika-Germaneau G, Serra W, Jaafari N, Chatard A. Forecasting a Fatal Decision: Direct Replication of the Predictive Validity of the Suicide-Implicit Association Test. Psychol Sci. 2020 Jan;31(1):65-74. doi: 10.1177/0956797619893062. Epub 2019 Dec 11.
- Background: PubMed 31481688Light SN, Bieliauskas LA, Taylor SF. Measuring change in anhedonia using the "Happy Faces" task pre- to post-repetitive transcranial magnetic stimulation (rTMS) treatment to left dorsolateral prefrontal cortex in Major Depressive Disorder (MDD): relation to empathic happiness. Transl Psychiatry. 2019 Sep 3;9(1):217. doi: 10.1038/s41398-019-0549-8.
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- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Brandon Bentzley, MD study director
Magnus Medical
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Active SAINT Stimulation in people with Major Depressive Disorder and Major Depressive Episode, run by Magnus Medical at 4 sites 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 17 inclusion and 20 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: stopped early, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Funding discontinued.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the neural network underlying Explicit Suicidal Cognition (ESC) as measured by resting state functional connectivity changes in subgenual anterior cingulate (sgACC) and the default mode network (DMN). (time frame: At baseline (day 0) and at post-inpatient treatment completion (day 2-7)). 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 NCT03693105, which also lists 14 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 24 Mar 2025.