Focal Electrically Administered Seizure Therapy for the Treatment of Depression

Treatment-Resistant Depression Clinical Trial

— FEAST  

Official title:

Investigating the Effects of Focal Electrically Administered Seizure Therapy (FEAST) for the Treatment of Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02462551
• Other study ID #: 21024/ PSY.ZN.03
• Status: Recruiting
• Phase: N/A
• First received: June 2, 2015
• Last updated: April 5, 2016
• Start date: September 2013
• Est. completion date: December 2016

Study information

• Verified date: April 2016
• Source: American University of Beirut Medical Center
• Contact: Ziad Nahas, MD, MSCR
• Phone: 00961-1-350000
• Email: zn17[@]aub.edu.lb
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationLebanon: Institutional Review BoardLebanon: Ministry of Public Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy and any possible side effects of focal electrically administered seizure therapy (FEAST) as a treatment intervention for patients with recurrent and treatment resistant depression.

Description:

Recurrent and treatment resistant depression (TRD) has high morbidity and escalating costs for the healthcare system and society at large. Electroconvulsive therapy (ECT) remains the most effective acute antidepressant treatment for TRD, but with significant risks of cognitive impairment. The efficacy and side effects of conventional ECT are contingent on the anatomic positioning of electrodes and stimulus dosage. A technique that could spatially target the prefrontal cortex may preserve the efficacy of ECT while simultaneously reducing cognitive side effects.

The investigators have recently demonstrated that focal electrically-administered seizure therapy [FEAST], which markedly improves the spatial targeting of the electrical current, is feasible in adult TRD individuals. FEAST can initiate seizures focally and specifically in the prefrontal cortex prior to secondary seizure generalization. Preliminary results in depressed humans at Columbia University and later at the Medical University of South Carolina (MUSC) generated by the PI (Nahas) show that these focal seizures produce clinically meaningful antidepressant responses. Additional work is needed to refine the technique and compare it to conventional approaches.

In this study, the investigators will further develop FEAST to achieve clinically meaningful remission rates (at least 50% of subjects). 30 TRD patients (or 20 with a complete record) will undergo an open-label course of FEAST for an adaptive number of total sessions designed to maximize efficacy of the technique. The investigators will use a dosing paradigm using a current level of 800 mA, finalize the electrode sizes, and test, at one treatment session, the effects of reversing the directionality of current flow on site of seizure induction. Patients will also undergo electroencephalography (EEG) assessments to characterize the induced seizures' spatial and temporal distributions. The investigators will obtain time to orientation recovery as a marker of potential longer-term cognitive side effects.

This technique could fundamentally change and improve the most effective antidepressant treatment, while simultaneously minimizing or eliminating the major side-effects that prohibit larger adoption of ECT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 90 years (inclusive)

• Diagnosis of major depressive disorder (unipolar or bipolar) [SCID to derive RDC; DSM-IV]

• Pretreatment HRSD score = 18 [Hamilton Rating Scale for Depression (24-item)]

• ECT indicated [Physician evaluation]

• Willing and capable of providing informed consent [Physician evaluation]

Exclusion Criteria:

• History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder [SADS to derive RDC; rapid cycling defined as = four episodes in past year]

• History of neurological illness or insult other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia) [Physician evaluation; medical history]

• Alcohol or substance abuse or dependence in the past year (RDC) [Physician evaluation]

• Secondary diagnosis of a delirium, dementia, or amnestic disorder (DSM-IV), pregnancy, or epilepsy [Physician evaluation]

• Requires especially rapid antidepressant response due to suicidality, psychosis, inanition, psychosocial obligations, etc. [Physician evaluation]

• Unable to tolerate psychotropic washout and no psychotropic medication during the ECT trial, other than lorazepam (up to 3 mg/d PRN) [Treatment history and physician evaluation]

• ECT in the past six months [Physician evaluation; medical history]

• Has a cardiovascular and/or pulmonary condition [Physician evaluation]

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment-Resistant Depression

Intervention

Device:
• Focal Electrically Administered Seizure Therapy
A focal administration of the right unilateral configuration of electro-convulsive therapy for the treatment of recurrent and treatment-resistant depression.

Locations

Country	Name	City	State
Lebanon	American University of Beirut Medical Center	Beirut

Sponsors (4)

Lead Sponsor	Collaborator
Ziad Nahas	Columbia University, MECTA corporation, Medical University of South Carolina

Country where clinical trial is conducted

Lebanon, 

References & Publications (9)

Chahine G, Short B, Spicer K, Schmidt M, Burns C, Atoui M, George MS, Sackeim HA, Nahas Z. Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST). Brain Stimul. 2014 May-Jun;7(3):483-5. doi: 10.1016/j.brs.2014.02.011. Epub 2014 Feb 22. — View Citation

George MS, Nahas Z, Li X, Kozel FA, Anderson B, Yamanaka K, Chae JH, Foust MJ. Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS). Semin Clin Neuropsychiatry. 2002 Oct;7(4):293-304. Review. — View Citation

Kayser S, Bewernick BH, Grubert C, Hadrysiewicz BL, Axmacher N, Schlaepfer TE. Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression. J Psychiatr Res. 2011 May;45(5):569-76. doi: 10.1016/j.jpsychires.2010.09.008. Epub 2010 Oct 16. — View Citation

Lisanby SH, Maddox JH, Prudic J, Devanand DP, Sackeim HA. The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry. 2000 Jun;57(6):581-90. — View Citation

Luber B, Nobler MS, Moeller JR, Katzman GP, Prudic J, Devanand DP, Dichter GS, Sackeim HA. Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. II. Topographic analyses. J ECT. 2000 Sep;16(3):229-43. — View Citation

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. — View Citation

Nobler MS, Luber B, Moeller JR, Katzman GP, Prudic J, Devanand DP, Dichter GS, Sackeim HA. Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. I. Global analyses. J ECT. 2000 Sep;16(3):211-28. — View Citation

Sackeim HA, Luber B, Moeller JR, Prudic J, Devanand DP, Nobler MS. Electrophysiological correlates of the adverse cognitive effects of electroconvulsive therapy. J ECT. 2000 Jun;16(2):110-20. — View Citation

Spellman T, Peterchev AV, Lisanby SH. Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction. Neuropsychopharmacology. 2009 Jul;34(8):2002-10. doi: 10.1038/npp.2009.12. Epub 2009 Feb 18. Erratum in: Neuropsychopharmacology. 2012 Mar;37(4):1077. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spatial and temporal distribution and power of induced seizure on EEG recordings	EEG recordings will be analyzed to assess the dynamics and characteristics of induced seizure activity; including spatial and temporal distribution, power, and current density in different cortical areas	15 min before to 5 min after stimulus delivery for the first 3 sessions in a maximum period of two weeks	No
Secondary	Change in Depression Scores	24-item Hamilton Depression Rating Scale	Baseline and 4-6 weeks	No
Secondary	Time for Reorientation	Five questions are asked after waking up from anesthesia to assess short and long-term memory.	30 minutes	No