Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy

NCT06529029 | Recruiting Phase 2 FDA Device

• 1 other identifier: STUDY00010089
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol proposes an initial randomized clinical trial that includes all patients with suicidal ideation (SI) at baseline, and with SI as the primary outcome measure to examine whether Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) treatment has more magnitude and rate of remission of SI as conventional pulse amplitude Right Unilateral Electroconvulsive Therapy (RUL ECT) (based on our prior secondary analysis). Our central hypothesis is that RUL LAP-ST has significantly less cognitive/memory side effects (no memory side effects were noted in our prior studies for 500mA and 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.

Conditions

Suicidal Ideation; Major Depressive Disorder; Schizo Affective Disorder; Bipolar Disorder

Keywords

Suicidal Ideation; Suicide; Depression; Major Depressive Disorder; Schizo Affective Disorder; Bipolar Disorder; Low Amplitude Seizure Therapy; Electroconvulsive Therapy; Neuromodulation; Brain Stimulation

Outcome Measures

Primary Outcomes (2)

• Suicide Ideation - Self Report

  Beck Scale for Suicide Ideation (SSI-Worst and SSI-Current) - self reported. Minimum score of 0, maximum score of 42. Lower score indicates a better outcome.

  Through study completion, an average of four weeks

• Suicide Ideation - Clinician Rated

  Columbia Suicide Severity Rating Scale (C-SSRS) - clinician administered. Intensity of suicidal ideation: minimum score of 0, maximum score of 5. Lower score indicates a better outcome. Suicidal behavior not rated on a scale.

  Through study completion, an average of four weeks

Secondary Outcomes (3)

• Depression - Clinician Rated

  Through study completion, an average of four weeks

• Depression - Self Report

  Through study completion, an average of four weeks

• Depression - Self Report

  Through study completion, an average of four weeks

Other Outcomes (7)

• Anxiety

  Through study completion, an average of four weeks

• Psychosis

  Through study completion, an average of four weeks

• Global Clinical Assessment

  Through study completion, an average of four weeks

Study Arms (2)

RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral)

EXPERIMENTAL

Low Amplitude Pulse Seizure Therapy RUL ECT at 600mA (or 700mA)

Device: Sigma-Stim

RUL ECT (Electroconvulsive Therapy)

ACTIVE COMPARATOR

RUL Conventional pulse amplitude Electroconvulsive Therapy (ECT)

Device: Sigma-Stim

Interventions

Sigma-Stim DEVICE

Right Ultra-Brief Low Amplitude Seizure Therapy at 600mA or 700mA vs Right Unilateral Ultra-Brief Standard ECT at 800mA.

RUL ECT (Electroconvulsive Therapy); RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients in whom ECT is clinically indicated: The referrals to ECT by the primary psychiatrist (before a consult by the ECT consultant) will serve to both increase the feasibility of the study and address any ethical concerns that the patient would not undergo ECT without having a valid full indication for the procedure as well as increase the external validity and generalizability of the study.
• Male or female patients 18 to 90 years of age
• Current DSM-5 criteria for MDE with any SI of major depressive, bipolar, or schizoaffective disorders
• Montgomery-Asberg depression rating scale (MADRS) with 2 or more on SI item
• Use of effective method of birth control for women of child-bearing capacity
• Patient is medically stable
• No anticipated need to alter psychotropic medications for the duration of the study (except for urgent/emergent situations)
• Ability of patient to fully participate in the informed consent process

You may not qualify if:

• Unstable or serious medical condition that substantially increases risks of ECT or cognitive impairment
• Female patients who are pregnant or plan to be pregnant during the study or are breast-feeding
• History of neurological disorder if deemed by the treating ECT physician or PI to pose a significant risk with ECT, or if there is any metal in the head or history of known structural brain lesion or skull defect that is deemed to affect cognition or safe ECT treatment
• Implanted devices that make ECT unsafe
• Clinical presentation of delirium or dementia
• Active substance use disorders within 1 week of randomization
• ECT in the past 1 month or prior failure to respond to an adequate course of ECT as deemed by the ECT physician treating the patient or the PI

Sponsors & Collaborators

• Michigan State University: lead
• Pine Rest Christian Mental Health Services: collaborator

Study Sites (1)

Pine Rest Christian Mental Health Services

Grand Rapids, Michigan, 49548, United States

RECRUITING

Related Publications (20)

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  PMID: 29319473 BACKGROUND

• Curtin S, Warner M, Hedegaard H: Increase in suicide in the United States, 1999-2014. NCHS data brief no. 241. Hyattsville, MD: US Department of Health and Human Services, CDC, National Center for Health Statistics. https://www.cdc.gov/nchs/data/databriefs/db241.pdf. 2016

  BACKGROUND

• Kellner CH, Fink M, Knapp R, Petrides G, Husain M, Rummans T, Mueller M, Bernstein H, Rasmussen K, O'connor K, Smith G, Rush AJ, Biggs M, McClintock S, Bailine S, Malur C. Relief of expressed suicidal intent by ECT: a consortium for research in ECT study. Am J Psychiatry. 2005 May;162(5):977-82. doi: 10.1176/appi.ajp.162.5.977.

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• Sienaert P. Based on a True Story? The Portrayal of ECT in International Movies and Television Programs. Brain Stimul. 2016 Nov-Dec;9(6):882-891. doi: 10.1016/j.brs.2016.07.005. Epub 2016 Jul 20.

  PMID: 27522170 BACKGROUND

• McCall WV, Lisanby SH, Rosenquist PB, Dooley M, Husain MM, Knapp RG, Petrides G, Rudorfer MV, Young RC, McClintock SM, Mueller M, Prudic J, Greenberg RM, Weiner RD, Bailine SH, Youssef NA, McCloud L, Kellner CH; CORE/PRIDE Work Group. Effects of continuation electroconvulsive therapy on quality of life in elderly depressed patients: A randomized clinical trial. J Psychiatr Res. 2018 Feb;97:65-69. doi: 10.1016/j.jpsychires.2017.11.001. Epub 2017 Nov 16.

  PMID: 29195125 BACKGROUND

• Kulak-Bejda A, Bejda G, Waszkiewicz N. Mental Disorders, Cognitive Impairment and the Risk of Suicide in Older Adults. Front Psychiatry. 2021 Aug 25;12:695286. doi: 10.3389/fpsyt.2021.695286. eCollection 2021.

  PMID: 34512415 BACKGROUND

• Lara E, Olaya B, Garin N, Ayuso-Mateos JL, Miret M, Moneta V, Haro JM. Is cognitive impairment associated with suicidality? A population-based study. Eur Neuropsychopharmacol. 2015 Feb;25(2):203-13. doi: 10.1016/j.euroneuro.2014.08.010. Epub 2014 Aug 21.

  PMID: 25190638 BACKGROUND

• Fernandez-Sevillano J, Alberich S, Zorrilla I, Gonzalez-Ortega I, Lopez MP, Perez V, Vieta E, Gonzalez-Pinto A, Saiz P. Cognition in Recent Suicide Attempts: Altered Executive Function. Front Psychiatry. 2021 Jul 22;12:701140. doi: 10.3389/fpsyt.2021.701140. eCollection 2021.

  PMID: 34366931 BACKGROUND

• Rutter SB, Cipriani N, Smith EC, Ramjas E, Vaccaro DH, Martin Lopez M, Calabrese WR, Torres D, Campos-Abraham P, Llaguno M, Soto E, Ghavami M, Perez-Rodriguez MM. Neurocognition and the Suicidal Process. Curr Top Behav Neurosci. 2020;46:117-153. doi: 10.1007/7854_2020_162.

  PMID: 32860213 BACKGROUND

• Szanto K, Galfalvy H, Vanyukov PM, Keilp JG, Dombrovski AY. Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression. J Clin Psychiatry. 2018 Mar/Apr;79(2):17m11611. doi: 10.4088/JCP.17m11611.

  PMID: 29489076 BACKGROUND

• Deng ZD, Lisanby SH, Peterchev AV. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study. J Neural Eng. 2011 Feb;8(1):016007. doi: 10.1088/1741-2560/8/1/016007. Epub 2011 Jan 19.

  PMID: 21248385 BACKGROUND

• Peterchev AV, Rosa MA, Deng ZD, Prudic J, Lisanby SH. Electroconvulsive therapy stimulus parameters: rethinking dosage. J ECT. 2010 Sep;26(3):159-74. doi: 10.1097/YCT.0b013e3181e48165.

  PMID: 20805726 BACKGROUND

• Youssef N, Sidhom E: Examination of Cognitive Profile and Variability in the Current Amplitude Domain of Low Current Amplitude ECT in Society of Biological Psychiatry 69th Annual Meeting (Published in Biological Psychiatry 2014 supplement) New York, New York2014

  BACKGROUND

• Youssef NA, Sidhom E. Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man. J Affect Disord. 2017 Nov;222:1-6. doi: 10.1016/j.jad.2017.06.022. Epub 2017 Jun 16.

  PMID: 28667887 BACKGROUND

• Youssef NA, McCall WV, Ravilla D, McCloud L, Rosenquist PB. Double-Blinded Randomized Pilot Clinical Trial Comparing Cognitive Side Effects of Standard Ultra-Brief Right Unilateral ECT to 0.5 A Low Amplitude Seizure Therapy (LAP-ST). Brain Sci. 2020 Dec 13;10(12):979. doi: 10.3390/brainsci10120979.

  PMID: 33322138 BACKGROUND

• Youssef NA, Ravilla D, Patel C, Yassa M, Sadek R, Zhang LF, McCloud L, McCall WV, Rosenquist PB. Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial. Brain Sci. 2019 Apr 29;9(5):99. doi: 10.3390/brainsci9050099.

  PMID: 31035665 BACKGROUND

• Abbott CC, Quinn D, Miller J, Ye E, Iqbal S, Lloyd M, Jones TR, Upston J, Deng Z, Erhardt E, McClintock SM. Electroconvulsive Therapy Pulse Amplitude and Clinical Outcomes. Am J Geriatr Psychiatry. 2021 Feb;29(2):166-178. doi: 10.1016/j.jagp.2020.06.008. Epub 2020 Jun 17.

  PMID: 32651051 BACKGROUND

• Beck AT, Brown GK, Steer RA. Psychometric characteristics of the Scale for Suicide Ideation with psychiatric outpatients. Behav Res Ther. 1997 Nov;35(11):1039-46. doi: 10.1016/s0005-7967(97)00073-9.

  PMID: 9431735 BACKGROUND

• Beck AT, Kovacs M, Weissman A. Assessment of suicidal intention: the Scale for Suicide Ideation. J Consult Clin Psychol. 1979 Apr;47(2):343-52. doi: 10.1037//0022-006x.47.2.343. No abstract available.

  PMID: 469082 BACKGROUND

MeSH Terms

Conditions

Suicidal Ideation; Depressive Disorder, Major; Psychotic Disorders; Bipolar Disorder; Suicide; Depression

Condition Hierarchy (Ancestors)

Self-Injurious Behavior; Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders

Study Officials

• Nagy A Youssef, MD, PhD

  Pine Rest Christian Mental Health Services & Michigan State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nagy A Youssef, MD, PhD

CONTACT

616-281-6451; nagy.youssef@pinerest.org

Janelle M Kassien, LMSW

CONTACT

616-980-7516; janelle.kassien@pinerest.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President for Research; Director of Psychiatry and Behavioral Medicine Division -West Michican

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 31, 2024
• Study Start: July 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)