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

Phase 2

Recruiting

• Conditions: Schizo Affective Disorder; Suicidal Ideation; Major Depressive Disorder; Bipolar Disorder
• Interventions: Device: Sigma-Stim

• Registration Number: NCT06529029
• Lead Sponsor: Michigan State University

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.

Study Timeline

• Status Verified: 2024-07
• Study Start: 2024-07-03
• Study First Submitted: 2024-07-19
• Study First Submitted QC: 2024-07-26
• Last Update Submitted: 2024-07-30
• Study First Posted: 2024-07-31
• Last Update Posted: 2024-08-01
• Primary Completion: 2026-07-01
• Study Completion: 2026-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RUL ECT (Electroconvulsive Therapy)	Sigma-Stim	RUL Conventional pulse amplitude Electroconvulsive Therapy (ECT)
RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral)	Sigma-Stim	Low Amplitude Pulse Seizure Therapy RUL ECT at 600mA (or 700mA)

Primary Outcome Measures

Name	Time	Method
Suicide Ideation - Self Report	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.
Suicide Ideation - Clinician Rated	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.

Secondary Outcome Measures

Name	Time	Method
Depression - Clinician Rated	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.
Depression - Self Report	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.

Trial Locations

Locations (1)

Pine Rest Christian Mental Health Services; 🇺🇸 Grand Rapids, Michigan, United States