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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01725334
Recruitment Status : Withdrawn (No participants enrolled)
First Posted : November 12, 2012
Last Update Posted : August 3, 2015
Sponsor:
Collaborators:
University Health Network, Toronto
Schizophrenia Society of Ontario
Information provided by (Responsible Party):
Z. J. Daskalakis, Centre for Addiction and Mental Health

Tracking Information
First Submitted Date  ICMJE November 8, 2012
First Posted Date  ICMJE November 12, 2012
Last Update Posted Date August 3, 2015
Study Start Date  ICMJE September 2012
Estimated Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2012)
Schedule for the Assessment of Negative Symptoms (SANS) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2012)
Schedule for the Assessment of Negative Symptoms (SANS) [ Time Frame: 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 distrubance of attention.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
Official Title  ICMJE Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia; Negative Type
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Procedure: Deep Brain Stimulation
  • 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.
    Intervention: Procedure: Deep Brain Stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: July 31, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: November 9, 2012)
6
Estimated Study Completion Date  ICMJE December 2015
Estimated Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01725334
Other Study ID Numbers  ICMJE 078/2011
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Z. J. Daskalakis, Centre for Addiction and Mental Health
Study Sponsor  ICMJE Centre for Addiction and Mental Health
Collaborators  ICMJE
  • University Health Network, Toronto
  • Schizophrenia Society of Ontario
Investigators  ICMJE
Principal Investigator: Zafiris J Daskalakis, MD, PhD Centre for Addiction and Mental Health
PRS Account Centre for Addiction and Mental Health
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP