The Effects of Stanford Accelerated Intelligent Neuromodulation Therapy on Explicit and Implicit Suicidal Cognition

Depressive Disorder, Major Clinical Trial

Official title:

The Effects of Stanford Accelerated Intelligent Neuromodulation Therapy on Explicit and Implicit Suicidal Cognition

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03693105
• Other study ID #: 47771
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 7, 2021
• Est. completion date: September 30, 2025

Study information

• Verified date: May 2022
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the effects of an accelerated schedule of theta-burst stimulation, termed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), on the neural networks underlying explicit and implicit suicidal cognition in inpatients with major depressive disorder.

Description:

We recently developed a form of neuromodulation termed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). SAINT-induced remission is associated with significant reductions in the functional connectivity of the neural network underlying explicit suicidal cognition (between sgACC-DMN). This project aims to further elucidate the SAINT induced neural network changes underlying explicit suicidal cognition.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female, 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) or Bipolar Affective Disorder II (BAD-II) 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 Method155 (MSM).
• Endorses clinically significant explicit suicidal cognitions (score = 9 on the M-SSI and score = 6 on the BSS self-report).
• MADRS and HDRS-17 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.
• 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.

Exclusion Criteria:

• Pregnancy
• The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia
• 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)
• 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 aiTBS 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.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Suicide

Intervention

Device:
• Accelerated theta burst stimulation
Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) 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.
• Sham stimulation
Participants who are randomly assigned to this group will receive sham stimulation to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system.

Locations

Country	Name	City	State
United States	Stanford Hospital	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (14)

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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. — View Citation

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. — View Citation

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. Erratum in: Biol Psychiatry. 2014 Sep 1;76(5):430. — View Citation

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. — View Citation

Gärtner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Böker H, Hättenschwiler 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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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. Review. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the neural networks underlying hopelessness as measured by resting state functional connectivity changes of sgACC and medial orbitofrontal cortex (mOFC).	We will use resting state functional connectivity of sgACC to the mOFC using magnetic resonance imaging to assess connectivity patterns correlated with hopelessness.	At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Other	Change in the neural networks underlying anhedonia as measured by resting state functional connectivity changes of ACC and DMN.	We will use resting state functional connectivity of ACC to the DMN using magnetic resonance imaging to assess connectivity patterns correlated with anhedonia.	At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Primary	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	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.	At baseline (day 0) and at post-inpatient treatment completion (day 2-7)