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

NCT01725334 | Withdrawn Phase 1

• 1 other identifier: 078/2011
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Negative Type

Keywords

Schizophrenia; Negative Symptoms; Treatment Resistance; Deep Brain Stimulation; Electrical Stimulation; Mental Disorders; Brain Diseases; Neurologic Manifestations; Signs and Symptoms

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation

EXPERIMENTAL

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

Ventral Tegmental Area (VTA) Stimulation

EXPERIMENTAL

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

Interventions

Deep Brain Stimulation 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.

Also known as: DBS

Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation; Ventral Tegmental Area (VTA) Stimulation

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• University Health Network, Toronto: collaborator
• Schizophrenia Society of Ontario: collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Related 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

MeSH Terms

Conditions

Schizophrenia; Mental Disorders; Brain Diseases; Neurologic Manifestations; Signs and Symptoms

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Zafiris J Daskalakis, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Temerty Centre for Therapeutic Brain Intervention

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: November 12, 2012
• Study Start: September 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 3, 2015

Record last verified: 2015-07

Locations

CA (1)