Clinical trial NCT02377505: Deep Brain Stimulation in Treatment Resistant Schizophrenia
Official title: Deep Brain Stimulation in Treatment Resistant Schizophrenia: Randomized, Controlled, Crossover Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Refractory Schizophrenia
Keywords: Treatment-Resistant Schizophrenia
Deep Brain Stimulation
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
Collaborators: name: Fondo de Investigacion Sanitaria
First posted: 2015-03-03
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Positive and Negative Syndrome Scale for Schizophrenia (PANSS)
timeFrame: Changes from baseline score to 1-3 weeks scores and to fortnightly scores until the end of trial (12 months)
Secondary outcomes:
measure: Clinical Global Impression-Schizophrenia (CGI-SCH)
timeFrame: Changes from baseline score to 1-12 months scores
measure: Global Functioning Scale (GFS)
timeFrame: Changes from baseline score to 1-3 weeks scores and to 1-12 months scores
measure: Social Functioning Scale (SFS)
timeFrame: Changes from baseline score to 1-3 weeks scores and to 1-12 months scores
measure: Personal and Social Performance (PSP)
timeFrame: Changes from baseline score to 1-12 months scores
measure: Psychotic Symptom Rating Scales (PSYRATS)
timeFrame: Changes from baseline score to 1-12 months scores
measure: Scale for the Assessment of Negative Symptoms (SANS)
timeFrame: Changes from baseline score to 1-12 months scores
measure: Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Changes from baseline score to 1-12 months scores
measure: Performance-Based Skills Assessment (UPSA)
timeFrame: Changes from baseline score to 12 months score
measure: Neuropsychological Assessment
timeFrame: Changes from baseline score to 12 months score
measure: Cerebral metabolism (PET scans)
timeFrame: Changes from baseline scan to 6 and 12 months scans
measure: n-Back (fMRI scan)
timeFrame: Changes from baseline scan to 6 and 12 months scans
measure: Adverse events (AEs)
timeFrame: Changes from baseline score to 1-3 weeks scores and to fortnightly scores until the end of trial (12 months)
Other outcomes:
Locations:
city: Sant Boi de Llobregat
country: Spain
facility: FIDMAG Germanes Hospitalàries Research Foundation
state: Barcelona
city: Barcelona
country: Spain
facility: Department of Psychiatry. Hospital Santa Creu i Sant Pau
Study officials:
affiliation: Department of Psychiatry. Hospital Santa Creu i Sant Pau
name: Iluminada Corripio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Salgado-Lopez L, Pomarol-Clotet E, Roldan A, Rodriguez R, Molet J, Sarro S, Alvarez E, Corripio I. Letter to the Editor: Deep brain stimulation for schizophrenia. J Neurosurg. 2016 Jul;125(1):229-30. doi: 10.3171/2015.12.JNS152874. Epub 2016 Apr 22. No abstract available.
citation: Corripio I, Sarro S, McKenna PJ, Molet J, Alvarez E, Pomarol-Clotet E, Portella MJ. Clinical Improvement in a Treatment-Resistant Patient With Schizophrenia Treated With Deep Brain Stimulation. Biol Psychiatry. 2016 Oct 15;80(8):e69-70. doi: 10.1016/j.biopsych.2016.03.1049. Epub 2016 Mar 10. No abstract available.
citation: Corripio I, Roldan A, Sarro S, McKenna PJ, Alonso-Solis A, Rabella M, Diaz A, Puigdemont D, Perez-Sola V, Alvarez E, Arevalo A, Padilla PP, Ruiz-Idiago JM, Rodriguez R, Molet J, Pomarol-Clotet E, Portella MJ. Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial. EBioMedicine. 2020 Jan;51:102568. doi: 10.1016/j.ebiom.2019.11.029. Epub 2020 Jan 8.