Clinical trial NCT00565617: Epidural Cortical Stimulation for Depression
Official title: A Pilot Safety and Efficacy Study of Epidural Prefrontal Cortical Stimulation (EpCS) in Severe Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: depression
epidural
cortical stimulation
brain stimulation
treatment-resistant
deep brain stimulation
TMS
DBS
ECS
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Medtronic
name: National Alliance for Research on Schizophrenia and Depression
First posted: 2007-11-30
Enrollment: 5
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: We are currently monitoring participants that were implanted with Epidural Cortical Stimulators starting back in 2008. Primary investigation is completed, but they have implanted devices for investigational treatment of depression. We will keep the study open while they are monitored.
Primary purpose: TREATMENT

Brief summary: Objective: Chronic epidural cortical stimulation (ECS) involves the neurosurgical placement of an electric wire on the surface of the brain with intermittent activation. Over time, ECS modulates local and distal connected brain regions. It is being currently applied over the motor cortex to treat intractable pain. Because of the important role played by the medial prefrontal cortex in mood regulation, the goal of this study is to apply this minimally invasive neurostimulation modality over medial prefrontal cortex in severely ill depressed subjects who have failed all other attempts at treatment.

Detailed description: Hypothesis: Severely Treatment Resistant Unipolar Depressed Subjects with EpCS of medial prefrontal cortex will show a significant decrease in depression symptoms at 6 months post-implant when compared to baseline and to a matched control group treated with electroconvulsive therapy (ECT).

Method: We will enroll 5 subjects with severe refractory depression in an open trial with a 1 month placebo lead in, and for up to 1 years. We will also naturalistically follow 5 matched control patients treated with ECT. Depressive and cognitive symptoms will be rated periodically to assess the safety and efficacy of this procedure.

Significance: This study takes advantage of the expertise at MUSC with various neuromodulation technologies to begin answering the crucial role of targeted cortical brain stimulation and its potential role in treatment resistant depression. This is a crucial pilot study that might lead to an entire new class of therapies for depression.

Eligibility criteria: Inclusion Criteria:

To be eligible for this study, a subject must meet all the following inclusion and exclusion criteria:

* Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior episodes) depression and is currently experiencing a major depressive episode without psychotic features as defined by DSM IV criteria.
* Subjects may have a diagnosis or unipolar or bipolar depressive episode.
* Subject has not had an adequate response to 4 or more adequate antidepressant treatments in the current depressive episode according to the Antidepressant Treatment History Form (ATHF) (Sackeim et al 1997).
* Subject must be between the ages of 21 and 80.
* Baseline HDRS 24-item ≥ 20 (both visits 1 week apart)
* Subject must be able to complete the evaluations needed for this study including the functional imaging scans.
* Subject must have had a history of one successful course of ECT in the past.
* Subject must provide written informed consent.
* Subject is stable on all antidepressant medication for at least 4 weeks before the baseline visit or not be taking antidepressant medication prior to entering the study.
* Subject must be able to remain on current medication schedule for the first 19 weeks of the study.
* Subject is not on a medication known to increase the risk of cortical stimulation-induced seizures. These include theophylline, stimulant medications, bupropion, or supraphysiological doses of thyroid supplements.

Exclusion Criteria:

The presence of any of the following will exclude a subject from the study:

* The EpCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient (including, but not limited to: history of serious cardiac or pulmonary problems, stroke, significant brain malformation, progressive neurological disease, central nervous system disease or injury, history of seizure, previous neurosurgical procedure with suspected brain tissue scarring that would increase the risks for seizure or cervical fracture).
* Subject received general anesthetic within the last 30 days prior to enrollment (not including ECT procedure).
* Subject currently has another investigational device or cardiac pacemaker, implantable defibrillator, or other implantable stimulator
* Subject on anticoagulant drugs, with low platelets counts or have PT or PTT abnormalities or other risk factors for intra-operative or post-operative bleeding
* Subject is expected to require full body magnetic resonance imaging (MRI) during the clinical study.
* Subject is judged by the investigator to be acutely suicidal (e.g. within the 30 days prior to the EpCS implant, the subject has made a suicide attempt or gesture or has made specific plans or preparation to commit suicide).
* Subject has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder, active substance abuse or dependence (with the exception to caffeine and nicotine abuse) or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM IV criteria.
* Subject with a diagnosis of dementia with a Mini-Mental State Exam (MMSE) ≤23.
* Female subjects with a positive urine pregnancy test.
* Subject with a positive urine drug screen or current alcohol or substance abuse other than nicotine and caffeine.

Primary outcomes:
measure: HDRS-24 Items
timeFrame: 7 months from baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Edward B Short, MD, MSCR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nahas Z, Anderson BS, Borckardt J, Arana AB, George MS, Reeves ST, Takacs I. Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):101-9. doi: 10.1016/j.biopsych.2009.08.021.
citation: Williams NR, Short EB, Hopkins T, Bentzley BS, Sahlem GL, Pannu J, Schmidt M, Borckardt JJ, Korte JE, George MS, Takacs I, Nahas Z. Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression. Brain Stimul. 2016 Nov-Dec;9(6):897-904. doi: 10.1016/j.brs.2016.06.054. Epub 2016 Jun 28.