Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy (LAP-ST vs ECT)

September 10, 2025 updated by: Nagy Youssef, MD, PhD, Michigan State University

Efficacy of Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy in Remission of Suicidal Ideation

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Michigan
      • Grand Rapids, Michigan, United States, 49548
        • Recruiting
        • Pine Rest Christian Mental Health Services
        • Principal Investigator:
          • Nagy A Youssef, MD, PhD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral)
Low Amplitude Pulse Seizure Therapy RUL ECT at 600mA (or 700mA)
Device: Sigma-Stim
Right Ultra-Brief Low Amplitude Seizure Therapy at 600mA or 700mA vs Right Unilateral Ultra-Brief Standard ECT at 800mA.
Active Comparator: RUL ECT (Electroconvulsive Therapy)
RUL Conventional pulse amplitude Electroconvulsive Therapy (ECT)
Device: Sigma-Stim
Right Ultra-Brief Low Amplitude Seizure Therapy at 600mA or 700mA vs Right Unilateral Ultra-Brief Standard ECT at 800mA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Suicide Ideation - Self Report
Time Frame: Through study completion, an average of four weeks
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
Time Frame: Through study completion, an average of four weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Depression - Clinician Rated
Time Frame: Through study completion, an average of four weeks
Montgomery-Asberg Depression Rating Scale (MADRS) - clinician administered. Minimum score of 0, maximum score of 60. Lower score indicates better outcome.
Through study completion, an average of four weeks
Depression - Self Report
Time Frame: Through study completion, an average of four weeks
Patient Health Questionnaire (PHQ9) - self reported. Minimum score of 0, maximum score of 27. Lower score indicates better outcome.
Through study completion, an average of four weeks
Depression - Self Report
Time Frame: Through study completion, an average of four weeks
Quick Inventory of Depressive Symptomatology (QIDS-SR) - self reported. Minimum score of 0, maximum score of 27. Lower score indicates better outcome.
Through study completion, an average of four weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anxiety
Time Frame: Through study completion, an average of four weeks
Generalized Anxiety Disorder (GAD7) - self reported. Minimum score 0, maximum score 21. Lower score indicates better outcome.
Through study completion, an average of four weeks
Psychosis
Time Frame: Through study completion, an average of four weeks
Positive and Negative Syndrome Scale (PANSS) - clinician administered. Full scale minimum score of 31. Maximum score of 217. Lower score indicates better outcome.
Through study completion, an average of four weeks
Global Clinical Assessment
Time Frame: Through study completion, an average of four weeks
Clinical Global Improvement (CGI) - clinician administered. Severity: minimum score of 0, maximum score of 7, lower score indicates better outcome. Improvement: minimum score of 0, maximum score of 7, lower score indicates better outcome.
Through study completion, an average of four weeks
Time to Reorientation after ECT sessions
Time Frame: Through study completion, an average of four weeks
Time to Reorientation scale (TRO) - study staff administered. Minimum score 3 minutes, maximum score more than 20 minutes. Lower score indicates better outcome.
Through study completion, an average of four weeks
Cognitive function and cognitive side effects
Time Frame: At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
Hopkins Verbal Learning Test-Revised (HVLTR) - clinician administered. Minimum score of 0, maximum score of 12. Higher score indicates better outcome.
At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
Cognitive Executive functions
Time Frame: At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
Delis Kaplan Executive Function Scale (DKEFS) - verbal fluency and color/word interference modules - clinician administered. Verbal fluency: minimum score of 1, maximum score of 60. Higher scores indicate better outcome for the total score. Color-word interference: minimum score of 1, maximum score of 19. In general, higher score indicate better outcome.
At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
Autobiographic Memory side effects
Time Frame: At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks
Autobiographic Memory Interview-Short Form (AMI-SF) - clinician administered. Minimum score of 0, maximum score of 30. Higher score indicates better outcome.
At baseline and completion of the acute ECT/LAP-ST course, an average of four weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michigan State University

Collaborators

Pine Rest Christian Mental Health Services

Investigators

  • Principal Investigator: Nagy A Youssef, MD, PhD, Pine Rest Christian Mental Health Services & Michigan State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 3, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

July 19, 2024

First Submitted That Met QC Criteria

July 26, 2024

First Posted (Actual)

July 31, 2024

Study Record Updates

Last Update Posted (Estimated)

September 16, 2025

Last Update Submitted That Met QC Criteria

September 10, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00010089

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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