The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition

NCT03693105 | Terminated Phase 2 DMC FDA Device

• 2 other identifiers: CLN-0105R01MH125160
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief 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 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.

Conditions

Major Depressive Disorder; Major Depressive Episode; Suicidal Ideation

Keywords

Suicidality; Neuromodulation; Transcranial magnetic stimulation; Depression; Intermittent theta burst stimulation

Outcome Measures

Primary Outcomes (1)

• 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.

  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).

  At baseline (day 0) and at post-inpatient treatment completion (day 2-7)

Other Outcomes (1)

• Change in the neural networks underlying depression, hopelessness and anhedonia as measured by resting state functional connectivity changes of sgACC and medial orbitofrontal cortex (mOFC).

  At baseline (day 0) and at post-inpatient treatment completion (day 2-7)

Study Arms (2)

SAINT stimulation

ACTIVE COMPARATOR

Active SAINT stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC)

Device: Active SAINT Stimulation

Sham stimulation

SHAM COMPARATOR

Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC)

Device: Sham SAINT Stimulation

Interventions

Active SAINT Stimulation DEVICE

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.

SAINT stimulation

Sham SAINT Stimulation DEVICE

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.

Sham stimulation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Magnus Medical: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (4)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Weill Cornell Medicine

Manhattan, New York, 10021, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

University of Texas, Austin

Austin, Texas, 78712, United States

Location

Related Publications (14)

• 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.

  PMID: 20439832 BACKGROUND

• George 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.

  PMID: 8547583 BACKGROUND

• Pascual-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.

  PMID: 8684201 BACKGROUND

• Abdallah 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.

  PMID: 27604566 BACKGROUND

• Liston 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.

  PMID: 24629537 BACKGROUND

• Green 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.

  PMID: 26717528 BACKGROUND

• Ballard 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.

  PMID: 30761601 BACKGROUND

• Tello 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.

  PMID: 31825760 BACKGROUND

• Light 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.

  PMID: 31481688 BACKGROUND

• Baeken 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.

  PMID: 29560909 BACKGROUND

• Downar 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.

  PMID: 24388670 BACKGROUND

• Duprat 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.

  PMID: 27378888 BACKGROUND

• Schmaal 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.

  PMID: 31787757 BACKGROUND

• Gartner 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.

  PMID: 30819549 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Suicidal Ideation; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Study Officials

• Brandon Bentzley, MD

  Magnus Medical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will receive either active or sham stimulation to the DLPFC. Patients will be randomized to either condition with a 50:50 chance.

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 2, 2018
• Study Start: June 30, 2024
• Primary Completion: March 6, 2025
• Study Completion: March 6, 2025
• Last Updated: March 24, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)