Evaluation of Tolcapone as a Cognitive Enhancer in Schizophrenia

NCT06387771 | Recruiting Phase 2 DMC

• 1 other identifier: rs4680-tolcapona
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Cognition; Pharmacogenetics; fMRI

Outcome Measures

Primary Outcomes (2)

• Efficacy: 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) .

  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.

  Day 8

Secondary Outcomes (9)

• Efficacy: change from baseline in psychotic symptoms intensity measured by the PANSS scores at day 8

  Day 8

• Efficacy: negative symptoms intensity: change from baseline in the 16-item Negative Symptom Assessment (NSA-16) scale scores at day 8

  Day 8

• Efficacy: change from baseline in the intensity of psychotic symptoms measured by the Brief Psychiatric Rating Scale (BPRS) scores at day 8

  Day 8

• Efficacy: change from baseline in the clinical global impression measured by the Clinical Global Impression (CGI) scale scores at day 8

  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

  Day 8

Other Outcomes (2)

• Patient Reported Outcome: change from baseline in the Profile of Mood States (POMS) scores at day 8

  Day 8

• Patient Reported Outcome: change from baseline in the mood state Visual Analogue Scale (VAS) scores at day 8

  Day 8

Study Arms (1)

Tolcapone

EXPERIMENTAL

Tolcapone (Film-coated tablet) 200 mg orally every 8 hours for 7 days

Drug: Tolcapone

Interventions

Tolcapone DRUG

Tolcapone (Film-coated tablet) 200 mg orally every 8 hours for 7 days

Tolcapone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Severe infections or diseases or hepatic failure (or increased liver enzymes), renal failure or bone marrow failure that advise against participation in the study at the investigator's discretion
• Positive pregnancy test, or breastfeeding women.
• Carriers of pacemaker or any kind of metallic prosthesis incompatible with magnetic resonance 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 causes psychiatric symptoms
• Cardiovascular disease and electrocardiogram alterations
• Patients receiving treatment with monoamine oxidase inhibitors during the study or up to 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 of Neuroleptic Malignant Syndrome and/or non-traumatic rhabdomyolysis or hyperthermia. Severe dyskinesia. Phaeochromocytoma. Hereditary galactose intolerance. Lapp lactase deficiency or glucose or galactose malabsorption.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead

Study Sites (1)

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitrophenols; Phenols; Ketones; Nitro Compounds

Study Officials

• Patricio Molero, MD, PhD

  Clinica Universidad de Navarra

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose Maria Galindo

CONTACT

34 948 255400; ucicec@unav.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2015
• First Posted: April 29, 2024
• Study Start: September 22, 2014
• Primary Completion: August 1, 2025
• Last Updated: April 29, 2024

Record last verified: 2024-02

Locations

ES (1)