Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia

Sponsor

Centre for Addiction and Mental Health (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01725334

Collaborator

University Health Network, Toronto (Other), Schizophrenia Society of Ontario (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Schizophrenia is a complex, challenging, and heterogeneous psychiatric condition, affecting up to 0.5% of the population and responsible for nearly 2% of all Canadian health-care expenditure. Much of the morbidity of the illness is related to its negative symptoms, including amotivation, asociality, anhedonia and flattened emotional affect, which lead to functional impairment and withdrawal from social and occupational domains. In contrast to positive symptoms, such as hallucinations and delusions, there are currently no effective treatments for negative symptoms, which experts recognize are largely responsible for the long-term disability of a majority of patients with schizophrenia. Advances in neuroscience have allowed a greater understanding of negative symptoms and have identified key structures and circuits believed to generate and maintain them. Here, we propose the application of a targeted therapy, deep brain stimulation, to alter the circuits driving negative symptoms.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Negative Type	Procedure: Deep Brain Stimulation	Phase 1

Detailed Description

Schizophrenia is a public health challenge with a large proportion of patients suffering from predominantly negative symptoms and who derive no benefit from currently available treatments. Advances in neuroscience have allowed a greater understanding of negative symptoms and have identified key structures and circuits believed to generate and maintain them. Here, we propose the application of a targeted therapy, deep brain stimulation (DBS), to alter the circuits driving negative symptoms. This is a phase I, non-blinded, non-randomized, pilot trial, exploring the safety and efficacy of DBS in patients with refractory negative symptoms of schizophrenia. Patients must be identified and approached by their treating psychiatrist regarding this study. Patients will be given several opportunities to review the study details with the investigators before the informed consent is presented. All eligible patients will also be reviewed by an independent non-study affiliated psychiatrist for confirmation of their diagnosis and assessment of study eligibility. The total study duration will be one year for each patient, who will undergo regular imaging and psychiatric analyses.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia

Study Start Date :

Sep 1, 2012

Anticipated Primary Completion Date :

Sep 1, 2015

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation The first 3 patients will have the DBS device target the NAcc/VS, which has been found to be hypoactive in patients with primarily negative symptoms.	Procedure: Deep Brain Stimulation Deep Brain Stimulation (DBS) is a surgical procedure involving the implantation of a thin flexible wire called a lead. This device sends mild electric signals to an area of the brain. This study targets two different areas that we believe may be responsible for negative symptoms observed in patients with schizophrenia. There are two stages to DBS: (1) Insertion of the DBS electrodes (2) The connection of these electrodes to a battery under the collarbone. Other Names: DBS
Experimental: Ventral Tegmental Area (VTA) Stimulation For 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms.	Procedure: Deep Brain Stimulation Deep Brain Stimulation (DBS) is a surgical procedure involving the implantation of a thin flexible wire called a lead. This device sends mild electric signals to an area of the brain. This study targets two different areas that we believe may be responsible for negative symptoms observed in patients with schizophrenia. There are two stages to DBS: (1) Insertion of the DBS electrodes (2) The connection of these electrodes to a battery under the collarbone. Other Names: DBS

Arm

Intervention/Treatment

Experimental: Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation

The first 3 patients will have the DBS device target the NAcc/VS, which has been found to be hypoactive in patients with primarily negative symptoms.

Procedure: Deep Brain Stimulation

Deep Brain Stimulation (DBS) is a surgical procedure involving the implantation of a thin flexible wire called a lead. This device sends mild electric signals to an area of the brain. This study targets two different areas that we believe may be responsible for negative symptoms observed in patients with schizophrenia. There are two stages to DBS: (1) Insertion of the DBS electrodes (2) The connection of these electrodes to a battery under the collarbone.

Other Names:

DBS

Experimental: Ventral Tegmental Area (VTA) Stimulation

For 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms.

Procedure: Deep Brain Stimulation

Other Names:

DBS

Outcome Measures

Primary Outcome Measures

Schedule for the Assessment of Negative Symptoms (SANS) [Change from baseline (pre-operative) SANS scores at one-year follow-up]
Assessment of primary and enduring negative symptoms consisting of affective blunting, alogia, avolition, anhedonia/asociality and impairments in attention. It is numerically graded on a scale from 0 to 5; 0 being not at all present and 5 being severe.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or Female patients between the age of 25-65
DSM IV-TR diagnosis of Schizophrenia Predominant Negative Subtype, as determined by the SANS and the Schedule for the Deficit Syndrome (SDS)
Greater negative than positive scores on the Positive and Negative Symptoms of Schizophrenia Scale (PANSS)
Confirmation of diagnosis by independent, non-study affiliated psychiatrist
Disease duration of > 5 years
Failure of medical therapy, defined as follows:
Failure of a minimum of three anti-psychotic treatments for specifically negative symptoms of schizophrenia (including clozapine)
No underlying neurological disease - No other active Axis I or Axis II co-morbidity that is the focus of clinical attention
Able to give informed consent: i)Deemed competent by two independent psychiatrists (one study psychiatrist and one non-study psychiatrist); ii) Score of > 70 on MacCat-CR
Able to comply with all testing and follow-up visit requirements defined by the Study Protocol
Mini mental status examination (MMSE)score > 25
Pre-menopausal women must agree to use acceptable methods of birth control (radiation risk of PET)

Exclusion Criteria:

Alcohol or substance dependence or abuse within 6 months, excluding nicotine or caffeine.
Current suicidal ideation, plan or intent for self-harm.
A suicide attempt in the past 1 year
Diagnosis of Major Depressive Disorder or Bipolar Depression
Major medical illness, cardiac pacemaker/defibrillator, and other implanted stimulator
Likely to relocate or move to a location distant from the study site within one year of enrollment
Any contraindication to MRI or PET scanning
Inability to provide consent, as well as an inability to appreciate the details and risk of the trial's procedures; competence will be assessed by two independent psychiatrists (one study psychiatrist, and one non-study psychiatrist)