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

Schizophrenia; Negative Type Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01725334
• Other study ID #: 078/2011
• Status: Withdrawn
• Phase: Phase 1
• First received: November 8, 2012
• Last updated: July 31, 2015
• Start date: September 2012
• Est. completion date: December 2015

Study information

• Verified date: July 2015
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 60 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia
• Schizophrenia; Negative Type

Intervention

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.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	Schizophrenia Society of Ontario, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Change from baseline (pre-operative) SANS scores at one-year follow-up	No

External Links

•   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