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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Centre for Addiction and Mental Health
Sponsor:
Collaborators:
University Health Network, Toronto
Schizophrenia Society of Ontario
Information provided by (Responsible Party):
Z. J. Daskalakis, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01725334
First received: November 8, 2012
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Schizophrenia; Negative Type
Procedure: Deep Brain Stimulation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Schedule for the Assessment of Negative Symptoms (SANS) [ Time Frame: Change from baseline (pre-operative) SANS scores at one-year follow-up ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 6
Study Start Date: September 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: DBS

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.

  Eligibility

Ages Eligible for Study:   25 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725334

Contacts
Contact: Laura Stefanik, BA 416-535-8501 ext 30157 laura.stefanik@camh.ca
Contact: Nir Lipsman, MD 416-603-6200 nir.lipsman@mail.utoronto.ca

Locations
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M6J 1H4
Contact: Laura Stefanik, BA    416-535-8501 ext 30157    Laura.stefanik@camh.ca   
Contact: Zafiris J Daskalakis, MD, PhD    416-535-8501 ext 34319    jeff.daskalakis@camh.ca   
Sponsors and Collaborators
Centre for Addiction and Mental Health
University Health Network, Toronto
Schizophrenia Society of Ontario
Investigators
Principal Investigator: Zafiris J Daskalakis, MD, PhD Centre for Addiction and Mental Health
  More Information

Additional Information:
No publications provided

Responsible Party: Z. J. Daskalakis, Chair, Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01725334     History of Changes
Other Study ID Numbers: 078/2011
Study First Received: November 8, 2012
Last Updated: May 1, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
Schizophrenia
Negative Symptoms
Treatment Resistance
Deep Brain Stimulation
Electrical Stimulation
Mental Disorders
Brain Diseases
Neurologic Manifestations
Signs and Symptoms

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014