Amplitude Titration to Improve ECT Clinical Outcomes

Amplitude Titration to Improve ECT Clinical Outcomes Randomized Clinical Trial

A randomized controlled trial will compare hippocampal neuroplasticity, antidepressant, and cognitive outcomes between individualized amplitude and fixed 800 mA amplitude ECT in older depressed subjects (n = 25 per group, n = 50 total). Relative to fixed 800 mA ECT:

H1: Individualized amplitude arm will have improved RUL antidepressant outcome (IDS-C30 response rates and reduced BT electrode placement switch at V2).

H2: Individualized amplitude arm will have improved cognitive outcomes (DKEFS-Verbal Fluency

Study Overview

• Status: Recruiting
• Conditions: Depression; Cognitive Change; ECT
• Intervention / Treatment: Device: Soterix Medical Incorporated 4x1 adapter; Device: Traditional ECT device

Detailed Description

ECT dosing can be divided into three categories for the ECT responder: insufficient (no antidepressant response, no cognitive impairment), optimal (antidepressant response, no cognitive impairment), or excessive (antidepressant response, cognitive impairment). Traditional fixed amplitude ECT dosing with 800 mA adjusts pulse train duration and frequency based on seizure titration or demographic factors (age, sex). Fixed amplitude produces variable electric fields and ECT dosing secondary to individual neuroanatomic differences. Adjustments to pulse width, pulse train duration, and frequency do not improve the efficacy of insufficient dosing or mitigate the cognitive risk of excessive dosing. In contrast, individualized amplitude based on electric field modeling or amplitude seizure titration produces consistent electric fields and ECT dosing. Based on our results from the R61 investigation, individualized amplitude with right unilateral electrode placement has the potential to reliably achieve optimal dosing and will be tested with the R33 phase of the investigation.

Subjects will receive baseline imaging, clinical (primary outcome: clinician rated Inventory of Depressive Symptomatology, IDS-C30), and neuropsychological assessment (primary outcome: Delis Kaplan Executive Function System Verbal Fluency, DKEFS) 24 to 48 hours prior to the first ECT session (V1). Subjects will receive their second assessment (V2) one day after the sixth ECT treatment and the final assessment (V3) one day after the ECT series. If the subject fails to demonstrate improvement at V2 (< 25% reduction from baseline IDS-C30 total score, the primary antidepressant outcome), the subject will then receive bitemporal (BT) electrode placement for the remainder of the ECT series. The transition to BT will be a secondary antidepressant outcome. Subjects will be randomized to receive right unilateral (RUL) electrode placement with an individualized amplitude (n = 25) or traditional fixed 800 mA amplitude (n = 25, 1:1 ratio). Subjects and Raters will be blinded to subject assignment. Subjects in both arms will receive fixed pulse width (1.0 milliseconds), frequency (20 hertz), and pulse train duration (8 seconds).

For the individualized amplitude arm, subjects will receive RUL amplitude determined seizure titration during the first treatment like the R61 phase of the investigation (IDE for Soterix adapter: G200123). Subsequent RUL treatments will be completed with an individualized amplitude. To determine the individualized amplitude, we will use Ebrain. The individualized amplitude can be determined from the optimal E-field (V/m) / baseline E-field (V/m per mA). If a discrepancy exists between the amplitude seizure and E-field modeling methods that results in amplitude difference > 100 mA, we will use the E-field modeling method to determine the individualized amplitude. We will round the amplitude to the nearest 100 mA from 500 to 900 mA (the current dosing range of the FDA approved ECT device).

For the fixed 800 mA amplitude arm, subjects will receive RUL amplitude determined seizure titration during the first treatment. The rationale for amplitude titration with the fixed amplitude arm is to 1) improve the goodness of fit of the amplitude-seizure and Ebrain relationship; and 2) control for a sub-therapeutic stimulation associated with the first treatment for both arms. RUL amplitude seizure titration will be conducted during the first treatment like the individualized amplitude arm. Subsequent RUL treatments will be completed with 800 mA amplitude. The only difference between the arms will be individualized versus fixed 800 mA amplitude after amplitude titration.

A randomized controlled trial will compare hippocampal neuroplasticity, antidepressant, and cognitive outcomes between individualized amplitude and fixed 800 mA amplitude ECT in older depressed subjects (n = 25 per group, n = 50 total). Relative to fixed 800 mA ECT:

H1: Individualized amplitude arm will have improved RUL antidepressant outcome (IDS-C30 response rates and reduced BT electrode placement switch at V2).

H2: Individualized amplitude arm will have improved cognitive outcomes (DKEFS-Verbal Fluency

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chris Abbott, MD; Phone Number: 5052720406; Email: cabbott@salud.unm.edu
• Study Contact Backup: Name: Megan Lloyd, MS; Phone Number: ‭(505) 272-3507‬; Email: meglloyd@salud.unm.edu

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87110
      • Recruiting
      • University of New Mexico Health Science Center
      • Contact: Chris Abbott, MD; Phone Number: 505-272-2223; Email: cabbott@salud.unm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of major depressive disorder or bipolar II
• Clinical indications for ECT with right unilateral electrode placement

Exclusion Criteria:

• Defined neurological or neurodegenerative disorder (e.g., traumatic brain injury, epilepsy, Alzheimer's disease)
• Other psychiatric conditions (e.g., schizophrenia, bipolar I disorder)
• Current drug or alcohol use disorder (except for nicotine)
• Contraindications to MRI.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Variable amplitude; Individualized amplitude	Device: Soterix Medical Incorporated 4x1 adapter; Device permits individualized amplitudes
Active Comparator: Fixed amplitude; Fixed (800 milliamperes) amplitude	Device: Traditional ECT device; FDA approved ECT device with fixed amplitude.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inventory of Depressive Symptomatology - Clinician Rated	Depression severity, scores from 0 to 84, higher scores indicate more depression severity	4 weeks
Delis Kaplan Executive Function System Letter Fluency	Cognitive measure, scale scores range from 0 to 20, higher scores indicate better cognitive performance	4 weeks

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Chris Abbott, MD, University of New Mexico

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: R33MH125126 (U.S. NIH Grant/Contract); 5R61MH125126 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be uploaded to National Data Archive.
• IPD Sharing Time Frame: Data will become available after study completion.
• IPD Sharing Access Criteria: National Data Archive guidelines.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes