Deep Brain Stimulation in Treatment Resistant Schizophrenia

Study Overview
=================
Brief Summary
-----------------
This study aims at assessing efficacy and safety of Deep Brain Stimulation (DBS) for treatment of patients with treatment resistant schizophrenia, by means of a random, controlled and crossed study.

Detailed Description
-----------------
The first phase of the study will consist of implanting electrodes. Recruited patients will be random to 2 targets: (1) medial prefrontal cortex (mPFC); (2) nucleus accumbens (NAcc). Continuous stimulation will be applied until the patients stabilise clinically. This period is anticipated between 6 and 9 months. After this stage, the next phase will consist of the crossover study. Those patients who respond to DBS will be randomly distributed in two groups, for a period of 3 months: on stimulation group and off stimulation group. Patients will then be crossed over to the other group for a further 3 months. Weekly visits during first month after, and fortnightly visits will be made during the entire study to evaluate treatment efficacy and patient tolerance. Patients who complete the study and respond to treatment with DBS will be provided continuing with treatment, and keeping control visits to assess the long-term effectiveness.

Official Title
-----------------
Deep Brain Stimulation in Treatment Resistant Schizophrenia: Randomized, Controlled, Crossover Pilot Study

Conditions
-----------------
Refractory Schizophrenia

Intervention / Treatment
-----------------
* Device: On-Stimulation
* Device: Off-Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged between 18 and 55 years. DSM IV-TR diagnosis of schizophrenia for at least 3 years prior to the screening visit. Determined to be treatment-resistant as demonstrated by: Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years. Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks. Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects. ECT is contraindicated or have failed to produce a maintained response. Persistence of positive symptoms defined as i) requiring a score of 4 (mild) or more on at least 2 of the next PANSS items: delusions, hallucinatory behavior, suspiciousness and unusual thought content; or as ii) requiring a score of 6 (severe) or more on at least 1 of the above PANSS items. Current CGI score 6 or more Stable antipsychotic treatment for last 2 months. Women of childbearing age using medically approved contraceptive methods. Adequate familiar or social support during all study procedures. Exclusion Criteria: MRI (Magnetic Resonance Imaging) contraindication to stimulation or contraindications for MRI History of epilepsy or clozapine-induced seizures, where use of anticonvulsants was needed Current suicidal ideation, plan or intent for self-harm during last 2 months. Evidence of global cognitive impairment. Current acute, serious or unstable illnesses. History of substance abuse (other than tobacco or caffeine). Comorbid axis I or II DSM IV-TR disorders. Female patients who are pregnant or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: On-Stimulation<br>Disease condition is assessed with stimulation turned on | Device: On-Stimulation<br>* The surgical electrode implanted in target 1 (mPFC) or target 2 (NAcc) by a pulse generating device (Kinetra, Medtronic Inc) is on<br>|
| Placebo Comparator: Off-Stimulation<br>Disease condition is assessed with stimulation turned off | Device: Off-Stimulation<br>* The surgical electrode implanted in target 1 (mPFC) or target 2 (NAcc) by a pulse generating device (Kinetra, Medtronic Inc) is off<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale for Schizophrenia (PANSS) | Scale to assess changes in schizophrenia' symptoms | Changes from baseline score to 1-3 weeks scores and to fortnightly scores until the end of trial (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression-Schizophrenia (CGI-SCH) | Scale to assess changes in schizophrenia symptoms' severity, global improvement or change. | Changes from baseline score to 1-12 months scores | 
| Global Functioning Scale (GFS) | Scale to assess changes in social, occupational, and psychological functioning | Changes from baseline score to 1-3 weeks scores and to 1-12 months scores | 
| Social Functioning Scale (SFS) | Scale to assess changes in social functioning | Changes from baseline score to 1-3 weeks scores and to 1-12 months scores | 
| Personal and Social Performance (PSP) | Scale to assess changes in functioning | Changes from baseline score to 1-12 months scores | 
| Psychotic Symptom Rating Scales (PSYRATS) | Scale to assess changes in hallucinations | Changes from baseline score to 1-12 months scores | 
| Scale for the Assessment of Negative Symptoms (SANS) | Scale to assess changes in negative symptoms of schizophrenia | Changes from baseline score to 1-12 months scores | 
| Calgary Depression Scale for Schizophrenia (CDSS) | Scale to assess changes in depressive symptoms | Changes from baseline score to 1-12 months scores | 
| Performance-Based Skills Assessment (UPSA) | Scale to assess changes in functional capacity | Changes from baseline score to 12 months score | 
| Neuropsychological Assessment | Battery of neuropsychological tests to assess changes in cognition | Changes from baseline score to 12 months score | 
| Cerebral metabolism (PET scans) | Assessment of changes in brain blow flow using the nuclear medicine procedure, PET | Changes from baseline scan to 6 and 12 months scans | 
| n-Back (fMRI scan) | Task to measure changes in working memory | Changes from baseline scan to 6 and 12 months scans | 
| Adverse events (AEs) | All unexpected medical problem that happens during DBS treatment | Changes from baseline score to 1-3 weeks scores and to fortnightly scores until the end of trial (12 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Treatment-Resistant Schizophrenia, Deep Brain Stimulation