Focal Electrically-Administered Seizure Therapy (FEAST) Studies at Two Enrolling Sites to Further Test and Refine the Treatment
Condition: Depression
MeSH terms: Seizures
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): FEAST; RUL UB
Intervention type(s): Device; Device
Intervention description(s): FEAST is a new form of ECT, with directional current, rather than traditional alternating current which goes in both directions between the electrodes.; This is right unilateral ultrabrief ECT, the standard of care.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Electroconvulsive Therapy