Enhanced Spatial Targeting in ECT Utilizing FEAST

• ClinicalTrials.gov Identifier: NCT04099342
• Recruitment Status: Recruiting
• First Posted: September 23, 2019
• Last Update Posted: March 17, 2023
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

The purpose of this research study is to find an alternative version of ECT that reduces the negative side effects (mainly memory loss) while still providing patients with relief from depressive symptoms. Previous forms of ECT may use Bilateral (electrodes on both sides of the head) or Right Unilateral (electrodes on one side of the head). Our research focuses on adjusting the placement of electrodes on one side of the head in order to better stimulate the Prefrontal Cortex (PFC) of the brain. By more specifically targeting the PFC, it is predicted that participants will receive the same benefit as ECT but will have fewer negative side effects after the treatment, mainly less memory loss. All other aspects of the treatment will be similar to regular, clinical ECT, including anesthesia and recovery monitoring. To accomplish this stimulation, an adjusted MECTA Spectrum 5000Q device will be used. If successful, this research study will demonstrate a way to improve ECT procedures for all patients suffering from Major Depressive Disorder by minimizing side effects and maintaining or improving efficacy.

Condition or disease	Intervention/treatment	Phase
Treatment Resistant Depression	Device: FEAST; Device: FEAST RP; Device: FEAST RC	Not Applicable

Detailed Description:

Study Design: This study will focus on refining FEAST methods by implementing a fixed-current titration and dosing method (800mA; 0.3 ms), testing the optimal directionality of current flow, and confirming specificity of induction of seizures in right orbitofrontal cortex. Twenty patients in an episode of major depression will be enrolled in the initial open-label study. Patients are kept on current medications for at least 2 weeks prior to initiation of therapy and throughout the treatment course. Patients are allowed PRN lorazepam limited to 3 mg/d but not within 10 hours of a FEAST session. Patients will undergo routine clinical care pre-ECT evaluations which include chemistry laboratory tests and an EKG. Patients may also undergo a brain MRI needed for 3D finite element modeling (FEM) to compute individual electric fields for each participant enrolled as well as a follow up MRI after treatment.

Once treatment is initiated, patients receive a dose 6 times initial Seizure Threshold (ST) at all treatments except the first, where ST is determined. If insufficient improvement (<40% change from baseline HRSD-24 item, or IDS-SR) after six treatments, the dose will increase by 50% in charge (9 times initial ST). Patients will undergo 6 channel EEG during all treatments. Sessions 2, 3 and 4 will be cross-randomized across FEAST (with typical electrodes placement and current flow directionality configurations), Revere Polarity FEAST and Reverse Configuration FEAST to allow a direct comparison of induced seizure focality. To ensure that each possible treatment sequence (ABC, ACB, BAC, BCA, CAB, CBA, where A=regular FEAST, B=RP FEAST, C=RC FEAST) during visits 2-4 is represented with approximately equal frequency, participants will be allocated to treatment sequence using a block randomization scheme with a block size of 6 participants. Within each block, each treatment sequence appears exactly once, in random order (e.g. 123456, 352641, etc.). In this way, the number of participants allocated to a particular sequence never differs by more than one from any other sequence.

The primary measure right frontal to motor connectivity (seizure drive) and time for orientation recovery obtained following these sessions will permit direct comparison between normal configuration, RP FEAST and RC FEAST as well. Preliminary data generated by the investigators suggest that RP polarity FEAST will elicit the most focal seizure with the shortest time for reorientation and fewest amnestic side effects.

Study Procedures:

A baseline appointment, scheduled at the Treatment Resistant Depression Clinic in Saint Louis Park, will be initially scheduled with potential participants to complete the informed consent process as well as baseline assessments for cognition, mood and quality of life. Participants may also undergo an optional baseline MRI that will consist of individual T1- and T2-weighted MRI scans which will be acquired with isotropic voxel resolution of 0.8 mm through resources located in the MIDB building. These structural data will be processed in the SimNIBS software to create a 3D volume conductor model of the subject's head. These MRI images will be constructed into 3D FEM models to compute non-invasive brain stimulation and electric fields for each participant enrolled.

All FEAST clinical procedures performed through Fairview will be documented in EPIC and duplicated in the research team's RedCap database for later analysis. Treatments are given in the morning, 3 times per week. Pharmacological agents are standardized: atropine (0.4 mg IV), methohexital (0.75 mg/kg) and succinylcholine (0.75-1.0 mg/kg). [If methohexital is unavailable, thiopental will be substituted (2.0 mg/kg]. Patients are oxygenated by mask (100% O2) prior to anesthesia and until resumption of spontaneous respiration. Standardized procedures are used to reduce impedance at ECT and EEG electrode sites. The d'Elia unilateral placement is used for conventional RUL ECT. FEAST will involve the 1.25" circular anterior electrode being centered at the measured FP2 position by the 10/20 EEG system, with the posterior cathode electrode (1"x2.5") tangential to the mid-sagittal plain and centered at vertex. FEAST is delivered with a modified MECTA Spectrum 5000Q relative to the commercial device with the capacity for unidirectional stimulation.

Follow up appointments halfway through the FEAST treatment series, 1-2 days after treatment, and 1 week after treatment will also be conducted. They will include assessments of cognition, mood and quality of life. A follow up MRI may also be conducted.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Enhanced Spatial Targeting in ECT Utilizing Focally Electrically-administered Seizure Therapy (FEAST)
• Actual Study Start Date: April 1, 2022
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: A: FEAST; Focally Electrically-administered Seizure Therapy (FEAST) is a form of Electroconvulsive therapy (ECT) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration.	Device: FEAST; FEAST with standard electrode configuration and current flow; Device: FEAST RP; FEAST with standard electrode configuration and reversed current flow; Device: FEAST RC; FEAST with standard current flow and reversed electrode configuration
Experimental: B: RP FEAST; Focally Electrically-administered Seizure Therapy (FEAST) with Reversed Polarity (RP) utilizes the same electrode placement as FEAST but a reversed directionality of current flow.	Device: FEAST; FEAST with standard electrode configuration and current flow; Device: FEAST RP; FEAST with standard electrode configuration and reversed current flow; Device: FEAST RC; FEAST with standard current flow and reversed electrode configuration
Experimental: C: RC FEAST; Focally Electrically-administered Seizure Therapy (FEAST) with Reversed Configuration (RC) utilizes the same current flow as FEAST but a reversed electrode configuration.	Device: FEAST; FEAST with standard electrode configuration and current flow; Device: FEAST RP; FEAST with standard electrode configuration and reversed current flow; Device: FEAST RC; FEAST with standard current flow and reversed electrode configuration

Outcome Measures

Primary Outcome Measures :

1. Seizure Drive Markers on EEG [ Time Frame: 8 weeks ]
   Electrophysiological markers of the induced seizure will be captured with a 6-lead EEG placed over bilateral frontal, temporal and parietal lobes. Raw data will be collected in MicroVolts while the analysis will summarize connectivity measures. Right prefrontal activity and seizure drive will be contrasted to other regions from which EEG is recorded, to describe the focality of FEAST-induced seizures.
2. Seizure characteristics on EEG [ Time Frame: 8 weeks ]
   Length of induced seizures is measured by EEG and recorded in seconds. Spectra powers, global and regional intensity will also be analyzed.
3. Seizure characteristics by motor observation [ Time Frame: 8 weeks ]
   Length of induced seizures is measured by motor observation and recorded in seconds. Spectra powers, global and regional intensity will also be analyzed.

Secondary Outcome Measures :

1. Change in Hamilton Depression Rating Score (HDRS) [ Time Frame: 8 weeks ]
   Change in HDRS from baseline to completion of each ECT treatment compared among 3 treatments - FEAST, FEAST RP, and FEAST RC. HDRS is a 24-item interview-based tool measuring depression symptoms in the previous week. Scoring is based on only the first 17 items. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Total scores are the sum of the 17 item scores and range from 0 (Normal functioning) to 22 (severe depression).
2. Change in Inventory for Depressive Symptoms - Self Report (IDS-SR) Score [ Time Frame: 8 weeks ]
   Change in IDS-SR scores from baseline to completion of each ECT treatment compared among 3 treatments - FEAST, FEAST RP, and FEAST RC. IDS-SR is a 30-item self report tool measuring depression symptoms in the previous week. Items are scored from 1 (normal functioning) to 3 (severely impaired) with some items scored on a yes (score of 1) or no (score of zero) basis. Items are summed to calculate the total score, which ranges from 0 (normal functioning) to 84 (severely impaired).
3. Time to Reorientation [ Time Frame: 8 weeks ]
   Time between subject open eyes immediately after procedure and correctly identifying 4 out of 5 questions on orientation to name, time and space will be noted in seconds.
4. Amnestic Side Effects [ Time Frame: 8 weeks ]
   Amnestic side effects will be determined via cognitive assessment and compared pre- and post-FEAST treatment.

Eligibility Criteria

• Ages Eligible for Study: 22 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of major depressive disorder using mini-7 to derive RDC; DSM-IV
• Pretreatment HRSC score greater than or equal to 18
• ECT indicated by physician evaluation
• Willing and capable of providing informed consent as determined by physician evaluation

Exclusion Criteria:

• History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder as determined by mini-7; rapid cycling defined as greater than or equal to four episodes in past year
• History of neurological illness or insult other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia) determined by physician evaluation and medical history
• Alcohol or substance abuse or dependence in the past year (RDC) determined by physician evaluation
• Secondary diagnosis of a delirium, dementia, or amnestic disorder (DSM-IV), pregnancy, or epilepsy determined by physician evaluation
• Requires especially rapid antidepressant response due to suicidality, psychosis, inanition, psychosocial obligations, etc. determined by physician evaluation
• ECT in the past six months determined by physician evaluation and medical history
• Pregnancy as determined by urine pregnancy test and clinical interview

Contacts and Locations

Contacts

Contact: Ziad Nahas, MD; 952-525-4505; znahas@umn.edu

Contact: Rachel Johnson, PhD; 952-525-4505; ipl@umn.edu

Locations

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Ziad Nahas, MSCR 952-525-4505 znahas@umn.edu

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Ziad Nahas, MD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04099342
• Other Study ID Numbers: PSYCH-2019-27591
• First Posted: September 23, 2019
• Last Update Posted: March 17, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Depressive Disorder, Treatment-Resistant; Depressive Disorder; Mood Disorders; Mental Disorders