Electroconvulsive Therapy Amplitude Titration

Not Applicable

Completed

Conditions: Major Depressive Disorder

Interventions: Device: Mecta Spectrum 5000Q paired with Soterix Medical 4X1 HD - ECT Multi-Channel Stimulation Interface

Registration Number: NCT04621786

Lead Sponsor: University of New Mexico

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental arm	Mecta Spectrum 5000Q paired with Soterix Medical 4X1 HD - ECT Multi-Channel Stimulation Interface	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.

Primary Outcome Measures

Name	Time	Method
Beta Coefficient From Linear Regression of Amplitude-determined Seizure (Independent Variable) and Ebrain (Dependent Variable)	First treatment	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.

Secondary Outcome Measures