Major Depressive Disorder
Conditions
Keywords
Electroconvulsive Therapy, Depressive Episode, Cognition
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.
Interventions
DEVICEMecta 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.
Sponsors
The Zucker Hillside Hospital
National Institute of Mental Health (NIMH)
The Mind Research Network
University of Texas Southwestern Medical Center
University of New Mexico
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Subject and outcomes assessor were blinded to amplitude titration
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Protocol Violation | 3 |
Baseline characteristics
| Characteristic | Experimental Arm |
|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 7.9 |
| Amplitude determined seizure | 312 milliamperes STANDARD_DEVIATION 113 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 1 / 29 |
Outcome results
Primary
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.
Time frame: First treatment
Population: Amplitude determined seizure (miliamperes) predicting Ebrain (Volts/meter per milliampere)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Experimental Arm | Beta Coefficient From Linear Regression of Amplitude-determined Seizure (Independent Variable) and Ebrain (Dependent Variable) | -.0001054 beta coefficient from linear regression |