Focal Electrically-Administered Seizure Therapy (FEAST) Studies at Two Enrolling Sites to Further Test and Refine the Treatment

NCT ID: NCT02535572

Last Updated: 2021-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2019-06-10

Brief Summary

This open label investigation further evaluates the safety, efficacy and potential mechanisms of action of a new form of electroconvulsive therapy (ECT). The investigators have recently completed preliminary open-label studies with FEAST, first at Columbia University, and then at the Medical University of South Carolina in Charleston (Nahas et al., 2013b). The investigators have published the outcomes of the first 17 patients studied. One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 + 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 + 6.8, 16.8 + 10.9; P < 0.0001). Eight of 16 patients met response criteria (≥50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24≤10). Patients achieved full re-orientation (4 of 5 items correct) in 5.5 + 6.4 min (median time = 3.6 min), timed from when their eyes first opened after treatment. The investigators have now studied 18 more patients (see results below), and we are completing the study in the original IDE with another two more patients still to enroll.

This work allowed us to refine the treatment. For example, the investigators selectively modified the electrode geometry to decrease interelectrode resistance. Additionally the investigators modified the titration schedule, now only administering a standard 800 ma ultrabrief pulse, and thus no longer titrating in the current domain.

In this next proposed trial we will continue to gather efficacy and safety data, and compare these to a parallel non-randomized group receiving ECT standard of care.

ECT is typically delivered in a dynamically adaptive manner, with each person having a different number of treatments, averaging between 8-12 treatment over 4-5 weeks. We thus have to use imprecise time points such as 'at the end of the acute treatment course' rather than specified dates or visits.

Detailed Description

This study will provide preliminary evaluation of the following:

1. Further characterization of the efficacy of FEAST and the safety of the treatment.

1. The primary efficacy measure will be the 24-item Hamilton Rating Scale for Depression. The changes in these scores from before to immediately following the treatment course (typically after 4 weeks) will be compared in patients treated with the FEAST methodology and matched to nonrandomized patients at our facilities who were treated with conventional ECT methods (ultrabrief right unilateral [RUL] ECT).

2. Acute and subacute cognitive side effects following FEAST will be assessed with a brief neuropsychological battery. The primary acute measures will be the time to return of orientation following seizure induction. The primary subacute measures will be assessment of retrograde amnesia for autobiographical information. The neuropsychological measures will be compared in the patients treated with the FEAST methodology (under this IDE) and matched (but nonrandomized) patients who are treated with conventional ECT methods (also covered under this IDE).

3. Safety will also be determined by examining the number and frequency of serious adverse advents and adverse events.

2. Characterization of the focal nature of the seizure onset with FEAST and RUL ECT. We will use two main methods to address the issue of focality.

1. Resting state fMRI before and after a course of FEAST (or conventional RUL ECT). We will address whether FEAST causes changes in hyper connected prefrontal cortical subcortical networks, and whether such an effect is more restricted to prefrontal cortex with FEAST relative to conventional RUL ECT.

2. Peri-ictal EEG acquired immediately before, during and immediately after the FEAST seizure. We will acquire this in all patients at all treatment sessions. Again, for comparison, we will use identical EEG acquisition methods in patients treated with conventional RUL ECT.

Conditions

Depression

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FEAST

Patients will receive the FEAST form of ECT

Group Type: EXPERIMENTAL

FEAST

Intervention Type: DEVICE

FEAST is a new form of ECT, with directional current, rather than traditional alternating current which goes in both directions between the electrodes.

RUL UB

Patients will receive the standard of care, right unilateral ultrabrief ECT (RUL UB)

Group Type: ACTIVE_COMPARATOR

RUL UB

Intervention Type: DEVICE

This is right unilateral ultrabrief ECT, the standard of care.

Interventions

FEAST

FEAST is a new form of ECT, with directional current, rather than traditional alternating current which goes in both directions between the electrodes.

Intervention Type: DEVICE

RUL UB

This is right unilateral ultrabrief ECT, the standard of care.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Major Depressive Episode
• Pretreatment Hamilton Depression Score >21
• ECT indicated
• Willing and able to give informed consent

Exclusion Criteria

• History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder
• History of central nervous system illness or insult other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia)
• Alcohol or substance abuse or dependence in the past year (DSM-V)
• Secondary diagnosis of a delirium, dementia, or amnestic disorder (DSM-V), pregnancy, or epilepsy
• Requires especially rapid antidepressant response due to suicidality, psychosis, inanition, psychosocial obligations, etc.
• No anticonvulsant mood stabilizers (e.g., Depakote, Tegretol, Lamictal); No lithium; No psychostimulants (e.g., Ritalin, Adderall);

Allowed medications during FEAST/ECT:

Antidepressants, including buproprion Atypical antipsychotics; Hypnotics for sleep; Anxiolytics (limited to up to 3 mg equivalents/day lorazepam)

• ECT in the past six months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Augusta University

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark S George, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Georgia Regents Medical Center

Augusta, Georgia, United States

Medical University of South Carolina Brain Stimulation Division

Charleston, South Carolina, United States

Countries

United States

References

Nahas Z, Short B, Burns C, Archer M, Schmidt M, Prudic J, Nobler MS, Devanand DP, Fitzsimons L, Lisanby SH, Payne N, Perera T, George MS, Sackeim HA. A feasibility study of a new method for electrically producing seizures in man: focal electrically administered seizure therapy [FEAST]. Brain Stimul. 2013 May;6(3):403-8. doi: 10.1016/j.brs.2013.03.004. Epub 2013 Mar 16.

Reference Type: BACKGROUND

PMID: 23518262 (View on PubMed)

Youssef NA, George MS, McCall WV, Sahlem GL, Short B, Kerns S, Manett AJ, Fox JB, Dancy M, Cook D, Devries W, Rosenquist PB, Sackeim HA. The Effects of Focal Electrically Administered Seizure Therapy Compared With Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy on Suicidal Ideation: A 2-Site Clinical Trial. J ECT. 2021 Dec 1;37(4):256-262. doi: 10.1097/YCT.0000000000000776.

Reference Type: DERIVED

PMID: 34015791 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00042678

Identifier Type: -

Identifier Source: org_study_id