Clinical trial NCT06529029: Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy
Official title: Efficacy of Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy in Remission of Suicidal Ideation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
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
Lead sponsor: Michigan State University
Sponsor class: OTHER
Collaborators: name: Pine Rest Christian Mental Health Services
First posted: 2024-07-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Suicide is one of the leading causes of mortality. Suicidal Ideation (SI) is a precursor to suicide. SI is especially hard to treat/remit in those with treatment-resistant psychiatric disorders (TRPD). This includes treatment-resistant mood disorders and psychotic disorders (such as schizophrenia and schizoaffective disorders). The above TRPD and the SI can remit with Electroconvulsive Therapy (ECT). That is to say, a transdiagnostic, evidence-based treatment for those patients, in addition to pharmacotherapy and psychotherapy, is ECT. ECT has both research support (mainly secondary analysis) and clinical evidence of a beneficial effect in remission of suicidality, as well as unsurpassed effect in treating primary mood and psychotic disorders including those who are treatment-resistant to other therapeutics. However, there are undeniable barriers to treatment with ECT. The most important barrier is memory side effects. ECT can help SI. ECT has also been shown to improve quality of life in a randomized trial by our group, which studied elderly patients with depression. Treating SI, along with the underlying disorder, especially in patients with TRPD is crucial in real-world patients who are clinically referred for ECT. These real-world referrals to ECT (by the patients' primary psychiatrist) will constitute the recruitment pool for this study.

Current amplitude drives electric fields to the deeper structures that are concerned with memory (Peterchev et al., 2010). Previously, the investigators performed the first in human proof of concept one arm open label clinical trial of LAP-ST, (N=22); followed by another small (N=7) pilot randomized, double-blinded clinical trial for the feasibility, safely and initial efficacy of LAP-ST, and another group later confirmed the more favorable cognitive side effects of LAP-ST compared to higher current amplitude (800mA).

However, efficacy of LAP-ST against suicidality has not been well established as primary outcome previously.

Thus, this protocol proposes an initial randomized clinical trial that includes all patients with SI at baseline, and with SI as the primary outcome measure to examine whether RUL LAP-ST treatment has more magnitude and rate of remission of SI as conventional pulse amplitude 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 or 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Male or female patients 18 to 90 years of age
3. Current DSM-5 criteria for MDE with any SI of major depressive, bipolar, or schizoaffective disorders
4. Montgomery-Asberg depression rating scale (MADRS) with 2 or more on SI item
5. Use of effective method of birth control for women of child-bearing capacity
6. Patient is medically stable
7. No anticipated need to alter psychotropic medications for the duration of the study (except for urgent/emergent situations)
8. Ability of patient to fully participate in the informed consent process

Exclusion Criteria:

1. Unstable or serious medical condition that substantially increases risks of ECT or cognitive impairment
2. Female patients who are pregnant or plan to be pregnant during the study or are breast-feeding
3. 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
4. Implanted devices that make ECT unsafe
5. Clinical presentation of delirium or dementia
6. Active substance use disorders within 1 week of randomization
7. 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

Primary outcomes:
measure: Suicide Ideation - Self Report
timeFrame: Through study completion, an average of four weeks
measure: Suicide Ideation - Clinician Rated
timeFrame: Through study completion, an average of four weeks
Secondary outcomes:
measure: Depression - Clinician Rated
timeFrame: Through study completion, an average of four weeks
measure: Depression - Self Report
timeFrame: Through study completion, an average of four weeks
measure: Depression - Self Report
timeFrame: Through study completion, an average of four weeks
Other outcomes:
measure: Anxiety
timeFrame: Through study completion, an average of four weeks
measure: Psychosis
timeFrame: Through study completion, an average of four weeks
measure: Global Clinical Assessment
timeFrame: Through study completion, an average of four weeks
measure: Time to Reorientation after ECT sessions
timeFrame: Through study completion, an average of four weeks
measure: Cognitive function and cognitive side effects
timeFrame: At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
measure: Cognitive Executive functions
timeFrame: At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
measure: Autobiographic Memory side effects
timeFrame: At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
Locations:
city: Grand Rapids
country: United States
facility: Pine Rest Christian Mental Health Services
state: Michigan
Study officials:
affiliation: Pine Rest Christian Mental Health Services & Michigan State University
name: Nagy A Youssef, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kochanek KD, Murphy S, Xu J, Arias E. Mortality in the United States, 2016. NCHS Data Brief. 2017 Dec;(293):1-8.
citation: 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
citation: 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.
citation: Fink M, Kellner CH, McCall WV. The role of ECT in suicide prevention. J ECT. 2014 Mar;30(1):5-9. doi: 10.1097/YCT.0b013e3182a6ad0d.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.