Objective: To assess the efficacy of tolcapone to improve cognition in schizophrenia, as a genotype-based targeted treatment of cognitive and negative symptoms of schizophrenia considering the polymorphism rs4680. Methodology: 20 patients with chronic and stabilized schizophrenia (10 patients with genotype Val/Val and 10 patients with genotype Met/Met according to polymorphism rs4680) will receive treatment with tolcapone during 7 days. The cognitive function and clinical status will be evaluated with a neuropsychological battery and appropriate clinical scales before and after treatment. The efficiency of the activation of the prefrontal cortex will be measured using functional magnetic resonance imaging (fMRI) before and after treatment. Hypothesis: Only patients with genotype Val/Val treated with tolcapone would show a cognitive improvement, a higher efficiency of the activation of the prefrontal cortex and an amelioration of some negative symptoms.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Tolcapone (Film-coated tablet) 200 mg orally every 8 hours for 7 days
Clinica Universidad de Navarra
Pamplona, Navarre, Spain
RECRUITINGEfficacy: Change from baseline in cognitive test scores at day 8
Performance in the cognitive tests scores: Dot Pattern Expectancy Task and cognitive tests (including subtests of the MATRICS\* battery) (\*MATRICS=Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive battery established by the National Institute of Mental Health) .
Time frame: Day 8
Efficacy: Change from baseline in the brain blood-oxygen-level-dependent (BOLD) response at day 8
Elicited brain activation during functional magnetic resonance neuroimaging (relative degree of activation of different brain regions) measured by BOLD signal.
Time frame: Day 8
Efficacy: change from baseline in psychotic symptoms intensity measured by the PANSS scores at day 8
Change in psychotic symptoms intensity measured by the PANSS symptom scores
Time frame: Day 8
Efficacy: negative symptoms intensity: change from baseline in the 16-item Negative Symptom Assessment (NSA-16) scale scores at day 8
Change in negative symptoms intensity measured by the NSA-16 scale
Time frame: Day 8
Efficacy: change from baseline in the intensity of psychotic symptoms measured by the Brief Psychiatric Rating Scale (BPRS) scores at day 8
Clinical outcome measured by the change in the scores on the BPRS
Time frame: Day 8
Efficacy: change from baseline in the clinical global impression measured by the Clinical Global Impression (CGI) scale scores at day 8
Clinical outcome measured by the change in the scores on the CGI scale
Time frame: Day 8
Efficacy: change from baseline in the global assessment of functioning measured by the Global Assessment of Functioning (GAF) scale scores at day 8
Clinical outcome measured by the change in the scores on the GAF scale
Time frame: Day 8
Efficacy: change from baseline in the anxiety symptoms measured by the Hamilton Anxiety Rating Scale (HAM-A) scale scores at day 8
Clinical outcome measured by the change in the scores on the HAM-A scale
Time frame: Day 8
Efficacy: change from baseline in the depressive symptoms measured by the Hamilton Depression Rating Scale (HAM-D) scale scores at day 8
Clinical outcome measured by the change in the scores on the HAM-D scale
Time frame: Day 8
Efficacy: change from baseline in the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scale scores at day 8
Clinical outcome measured by the change in the scores on the CRDPSS scale
Time frame: Day 8
Change from baseline in plasmatic homocysteine (umol/L)
Clinical outcome measured by the change in homocystinemia (umol/L)
Time frame: Day 8
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.