Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
Primary Purpose
Schizophrenia; Negative Type
Status
Withdrawn
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Deep Brain Stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia; Negative Type focused on measuring Schizophrenia, Negative Symptoms, Treatment Resistance, Deep Brain Stimulation, Electrical Stimulation, Mental Disorders, Brain Diseases, Neurologic Manifestations, Signs and Symptoms
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)
Sites / Locations
- Centre for Addiction and Mental Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation
Ventral Tegmental Area (VTA) Stimulation
Arm Description
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.
For 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms.
Outcomes
Primary Outcome Measures
Schedule for the Assessment of Negative Symptoms (SANS)
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01725334
First Posted
November 8, 2012
Last Updated
July 31, 2015
Sponsor
Centre for Addiction and Mental Health
Collaborators
University Health Network, Toronto, Schizophrenia Society of Ontario
1. Study Identification
Unique Protocol Identification Number
NCT01725334
Brief Title
Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
Official Title
Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Withdrawn
Why Stopped
No participants enrolled
Study Start Date
September 2012 (undefined)
Primary Completion Date
September 2015 (Anticipated)
Study Completion Date
December 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health
Collaborators
University Health Network, Toronto, Schizophrenia Society of Ontario
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia; Negative Type
Keywords
Schizophrenia, Negative Symptoms, Treatment Resistance, Deep Brain Stimulation, Electrical Stimulation, Mental Disorders, Brain Diseases, Neurologic Manifestations, Signs and Symptoms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation
Arm Type
Experimental
Arm Description
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.
Arm Title
Ventral Tegmental Area (VTA) Stimulation
Arm Type
Experimental
Arm Description
For 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms.
Intervention Type
Procedure
Intervention Name(s)
Deep Brain Stimulation
Other Intervention Name(s)
DBS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Schedule for the Assessment of Negative Symptoms (SANS)
Description
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.
Time Frame
Change from baseline (pre-operative) SANS scores at one-year follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zafiris J Daskalakis, MD, PhD
Organizational Affiliation
Centre for Addiction and Mental Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6J 1H4
Country
Canada
12. IPD Sharing Statement
Links:
URL
http://www.camh.ca/en/research/Pages/research.aspx
Description
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
Learn more about this trial
Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
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