Deep Brain Stimulation in Treatment Resistant Schizophrenia

Not Applicable

Completed

• Conditions: Refractory Schizophrenia
• Interventions: Device: On-Stimulation; Device: Off-Stimulation

• Registration Number: NCT02377505
• Lead Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

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.

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2015-02-26
• Study First Submitted QC: 2015-03-02
• Study First Posted: 2015-03-03
• Primary Completion: 2017-02
• Study Completion: 2019-12-23
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-17
• Last Update Posted: 2020-02-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. Male or female aged between 18 and 55 years.

2. DSM IV-TR diagnosis of schizophrenia for at least 3 years prior to the screening visit.

3. Determined to be treatment-resistant as demonstrated by:

   1. Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years.
   2. Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks.
   3. Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects.
   4. ECT is contraindicated or have failed to produce a maintained response.

4. 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.

5. Current CGI score 6 or more

6. Stable antipsychotic treatment for last 2 months.

7. Women of childbearing age using medically approved contraceptive methods.

8. Adequate familiar or social support during all study procedures.

Exclusion Criteria

1. MRI (Magnetic Resonance Imaging) contraindication to stimulation or contraindications for MRI
2. History of epilepsy or clozapine-induced seizures, where use of anticonvulsants was needed
3. Current suicidal ideation, plan or intent for self-harm during last 2 months.
4. Evidence of global cognitive impairment.
5. Current acute, serious or unstable illnesses.
6. History of substance abuse (other than tobacco or caffeine).
7. Comorbid axis I or II DSM IV-TR disorders.
8. Female patients who are pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
On-Stimulation	On-Stimulation	Disease condition is assessed with stimulation turned "on"
Off-Stimulation	Off-Stimulation	Disease condition is assessed with stimulation turned "off"

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

FIDMAG Germanes Hospitalàries Research Foundation; 🇪🇸 Sant Boi de Llobregat, Barcelona, Spain

Department of Psychiatry. Hospital Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain