Evaluation of Tolcapone as a Cognitive Enhancer in Schizophrenia

Phase

Condition

Psychosis

Tourette's Syndrome

Schizotypal Personality Disorder (Spd)

Treatment

Tolcapone

Clinical Study ID

NCT06387771

rs4680-tolcapona

Ages 18-65
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Ability to give informed consent and express the wish to fulfill all the requirementsof the protocol during the study period.
The patient must be capable of fulfillment of all the requirements of the clinicaltrial, at the investigator's discretion.
Patients diagnosed with schizophrenia according to the Diagnostic and StatisticalManual of Mental Disorders, 5th Edition (DSM-5). Only chronic patients will berecruited, and they must be clinically compensated in order to consent to participate.The determination of clinical compensation will be conducted according with thesecriteria: i) outpatients, with absence of hospitalization due to acute psychiatricdecompensation in the previous year, and ii) maintained GAF score equal or higher than 60 during the previous month. The recruitment process will include a clinicalinterview to verify the diagnosis.
Caucasic ethnicity
Negative pregnancy test for women of childbearing age.

Exclusion

Exclusion Criteria:

Severe infections or diseases or hepatic failure (or increased liver enzymes), renalfailure or bone marrow failure that advise against participation in the study at theinvestigator's discretion
Positive pregnancy test, or breastfeeding women.
Carriers of pacemaker or any kind of metallic prosthesis incompatible with magneticresonance imaging.
History of hypersensitivity to Tasmar® (tolcapone) or to any of its components
Active (in the last 12 months) substance abuse, or other disease that causespsychiatric symptoms
Cardiovascular disease and electrocardiogram alterations
Patients receiving treatment with monoamine oxidase inhibitors during the study or upto 15 days prior to the beginning of the study.
Patients receiving treatment with a catechol-O-methyltransferase (COMT) inhibitor
Participation in another clinical trial in the previous 30 days.
Other circumstances which involve Tasmar® (tolcapone) contraindications: history ofNeuroleptic Malignant Syndrome and/or non-traumatic rhabdomyolysis or hyperthermia.Severe dyskinesia. Phaeochromocytoma. Hereditary galactose intolerance. Lapp lactasedeficiency or glucose or galactose malabsorption.

Study Design