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

NCT ID: NCT01725334

Last Updated: 2015-08-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2015-12-31

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.

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.

Conditions

Schizophrenia; Negative Type

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

Deep Brain Stimulation

Intervention Type: PROCEDURE

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.

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.

Group Type: EXPERIMENTAL

Deep Brain Stimulation

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Other Intervention Names

DBS

Eligibility Criteria

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)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Schizophrenia Society of Ontario

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Z. J. Daskalakis

Chair, Temerty Centre for Therapeutic Brain Intervention

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zafiris J Daskalakis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

Related Links

http://www.camh.ca/en/research/Pages/research.aspx

Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre

Other Identifiers

078/2011

Identifier Type: -

Identifier Source: org_study_id