Schizophrenia; Negative TypePhase 1NCT01725334
Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
A Phase 1 study testing Deep Brain Stimulation in people with Schizophrenia; Negative Type, run by Centre for Addiction and Mental Health at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 25 to 60 years
- Conditions the study is for
- Schizophrenia; Negative Type
- What is being tested?
- Deep Brain Stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2012to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
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.
Read the 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.
- Conditions
- Schizophrenia; Negative Type
- Being tested
- Deep Brain Stimulation
- Keywords
- Schizophrenia, Negative Symptoms, Treatment Resistance, Deep Brain Stimulation, Electrical Stimulation, Mental Disorders, Brain Diseases, Neurologic Manifestations, Signs and Symptoms
- Medical subject headings
- Schizophrenia, Mental Disorders, Brain Diseases, Neurologic Manifestations, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep Brain StimulationProcedure or surgery
Also called DBS
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Deep Brain Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline (pre-operative) SANS scores at one-year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2012 (estimated)
- Study startSep 2012
- Primary completionSep 2015 (estimated)
- Study completionDec 2015 (estimated)
Why it stopped: No participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia; Negative TypeStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto, Schizophrenia Society of Ontario
- Responsible party
- Principal investigator, Z. J. Daskalakis, Centre for Addiction and Mental Health
- Investigators
- Zafiris J Daskalakis, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01725334
- Sponsor's protocol ID
- 078/2011
- Status last verified
- Jul 2015
- First submitted
- 8 Nov 2012
- Last updated
- 3 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia
- ClinicalTrials.gov ID
- NCT01725334
- Acronym / sponsor ID
- 078/2011
- Conditions
- Schizophrenia; Negative Type
- Keywords
- Schizophrenia, Negative Symptoms, Treatment Resistance, Deep Brain Stimulation, Electrical Stimulation, Mental Disorders, Brain Diseases, Neurologic Manifestations
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, Schizophrenia Society of Ontario
- Study start
- Sep 2012
- Primary completion
- Sep 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 12 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation | Experimental | Procedure: Deep Brain StimulationThe 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. |
| Ventral Tegmental Area (VTA) Stimulation | Experimental | Procedure: Deep Brain StimulationFor 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms. |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deep Brain StimulationAlso: DBSDeep 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. | Procedure or surgery | Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation, Ventral Tegmental Area (VTA) Stimulation |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2015.
- 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 CentreLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zafiris J Daskalakis, MD, PhD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Deep Brain Stimulation in people with Schizophrenia; Negative Type, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Schedule for the Assessment of Negative Symptoms (SANS) (time frame: Change from baseline (pre-operative) SANS scores at one-year follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2015.