Electroconvulsive Therapy Amplitude Titration

Electroconvulsive Therapy Amplitude Titration for Improved Clinical Outcomes in Late Life Depression

This study is focused on advancing ECT treatment for older adults with depressive disorders by refining neuromodulation stimulus parameters to improve efficacy and cognitive safety.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: Mecta Spectrum 5000Q paired with Soterix Medical 4X1 HD - ECT Multi-Channel Stimulation Interface

Detailed Description

Amplitude titration, as proposed in this current proposal, can reduce the variability related to fixed amplitude dosing and optimize clinical and cognitive outcomes. The goal of this project is to change standard ECT parameter selection from a fixed amplitude to an individualized and empirically determined amplitude. To achieve this goal, the investigators will focus on the relationship between amplitude titration and treatment-responsive changes in hippocampal neuroplasticity with RUL fixed amplitude ECT. Fixed amplitude ECT results in variable E-field or ECT dose. Over the course of an ECT series, the variable ECT dose will result in inconsistent changes in hippocampal neuroplasticity. In contrast, pre-translational investigations have demonstrated that amplitude titration results in a consistent E-field or ECT "dose". Seizure titration amplitudes (based on historic data, 233 to544mA) are below the amplitude range of FDA-approved ECT devices (500 to 900mA) and will require an adaptor to reduce the output amplitude (Investigational Device Exemption). Amplitude titration will also be below the hippocampal neuroplasticity threshold and insufficient for antidepressant response. The difference between RUL amplitude titration and RUL fixed amplitude (800mA) ECT will determine the degree of target engagement with the hippocampus. To illustrate, subjects with low amplitude titration of ~250 mA (800/250, high fixed/titration amplitude ratio) will have significant changes in hippocampal neuroplasticity. Subjects with high amplitude titration ~500mA (800/500, low fixed/titration ratio) will have minimal changes in hippocampal neuroplasticity. The relationship between amplitude titration and fixed amplitude hippocampal neuroplasticity will be used to develop the amplitude multiplier required for consistent and clinically effective ECT dosing.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher Abbott, MD; Phone Number: 5052723507; Email: cabbott@salud.unm.edu
• Study Contact Backup: Name: megan lloyd; Phone Number: 5052723507; Email: meglloyd@salud.unm.edu

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of major depressive disorder
• Clinical indications for ECT with right unilateral electrode placement
• Right-handed
• Age range between 50 and 80 years

Exclusion Criteria:

• Defined neurological or neurodegenerative disorder (e.g., traumatic brain injury, epilepsy, Alzheimer's disease)
• Other psychiatric conditions (e.g., schizophrenia, bipolar disorder)
• Current drug or alcohol use disorder (except for nicotine); and 4) contraindications to MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; All subjects enrolled will receive amplitude titration for their first treatment. The remainder of the ECT series will be completed with traditional (800mA) pulse amplitude with right unilateral electrode placement. This investigation only includes the single open-label arm.	Device: Mecta Spectrum 5000Q paired with Soterix Medical 4X1 HD - ECT Multi-Channel Stimulation Interface; The Mecta Spectrum 5000Q paired with Soterix Medical 4X1 HD-ECT Multi-Channel Stimulation Interface will reduce ECT current amplitude for amplitude-seizure titration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta Coefficient From Linear Regression of Amplitude-determined Seizure (Independent Variable) and Ebrain (Dependent Variable)	Electric field modeling is used to calculate Ebrain from the pre-ECT structural MRI. Ebrain is an individual's electric field strength (Volts/meter) per unit current (milliampere). To avoid confounds from the tissue boundary effects, Ebrain is calculated as the 90th percentile of maximal. Higher values (0.2 Volts/meter per milliampere) indicate that an individual receives a higher electric field strength per unit current. The Ebrain in this sample ranges from 0.1 to 0.19 Volts/meter per milliampere. Linear regression model assessed the relationship between amplitude-determined seizure (independent variable) and Ebrain (dependent variable) with beta coefficient and 95% confidence intervals.	First treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delis-Kaplan Executive Function System verbal fluency (DKEFS) test score	The DKEFS-VF is a neuropsychological measure of executive functioning. The scoring range (scaled scores) is between 1 to 19 with higher scores related to superior executive functioning.	The time frame is four weeks (before and after the ECT series).

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: National Institute of Mental Health (NIMH); University of Texas Southwestern Medical Center; The Mind Research Network; The Zucker Hillside Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: October 27, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cognition; Electroconvulsive Therapy; Depressive Episode
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: MH125126 (Other Grant/Funding Number: NIMH)

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