Evaluation of the Efficacy of Tolcapone as a Genotype-Based Targeted Cognitive Enhancer in Schizophrenia, Based on the Polymorphism RS4680

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Clinica Universidad De Navarra

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

completed 27 Apr 2026

Decision date (initial)

2024-05-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511433-35-00

EudraCT number

2010-024119-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To objectify the efficacy of Tolcapone, depending on the genotype for the rs4680 polymorphism of the COMT enzyme gene, to improve cognitive impairment and negative symptoms in patients with long-standing schizophrenia, in the clinical compensation phase.

Secondary objectives 4

1. To study the performance of patients with schizophrenia in cognitive tasks dependent on the prefrontal cortex, which require using the function of attention and context processing.
2. Determine the dysfunctional brain areas in patients with schizophrenia when performing these cognitive tasks.
3. Establish associations between the genotypes for the rs4680 polymorphism of the COMT enzyme gene and cognitive performance in the tasks administered to patients, searching for genetic profiles that may be prognostic markers in terms of cognitive functioning and response to pharmacological treatment of schizophrenia.
4. Correlate plasma concentrations of the drug with its pharmacological action.

Conditions and MedDRA coding

SCHIZOPHRENIA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ability to provide informed consent and express your desire to comply with all protocol requirements during the study period.
2. The patient must, in the opinion of the investigator, be able to comply with all the requirements of the clinical trial.
3. Age between 18-65 years.
4. Patients diagnosed with schizophrenia according to DSM-5. Only chronic patients will be recruited (disease duration greater than or equal to 5 years) and, in order to obtain informed consent for participation in this study, all patients must be in the clinical compensation phase at the time of recruitment. The determination of clinical compensation will be made according to these criteria: i) patients receiving treatment on an outpatient basis, with no hospitalization due to acute psychiatric decompensation during the previous year, and ii) score on the Global Activity Assessment Scale (GAF) maintained equal to or greater than 60 during the last month. The recruitment process will include a clinical interview to verify the diagnosis.
5. Caucasian origin
6. In the case of a woman of childbearing age, a negative pregnancy test.

Exclusion criteria 11

1. Infections or serious diseases or kidney or spinal cord failure that discourage the patient's participation in the study, according to the researcher's criteria
2. Liver alterations (increase in liver enzymes above normal values) that discourage the patient's participation in the study, according to the investigator's criteria
3. Positive pregnancy test, or breastfeeding women
4. Being a wearer of any metal prosthesis or pacemaker incompatible with performing nuclear magnetic resonance.
5. History of hypersensitivity to Tasmar® (Tolcapone) or any of its components.
6. Current history (in the last 12 months) of substance abuse or existence of another illness that justifies the appearance of psychiatric symptoms
7. Cardiovascular disease and clinically relevant ECG alteration
8. Patients who, during the study or up to 15 days before starting the study, receive or have received treatment with MAOIs
9. Patients receiving treatment with a COMT inhibitor
10. Participation in another clinical trial in the previous 30 days.
11. Other situations that imply contraindications for Tasmar® (Tolcapone): History of neuroleptic malignant syndrome or non-traumatic rhabdomyolysis or malignant hyperthermia. Severe dyskinesia. Pheochromocytoma. Hereditary lactose or galactase intolerance. Lapp lactase deficiency or glucose or galactose malabsorption.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Performance in the DPX cognitive test and in the modified MATRICS battery (number of errors and response times) 2) Brain activation elicited during functional brain MRI (fMRI) (relative degree of activation of different brain regions): BOLD response

Secondary endpoints 3

1. Efficacy: scores on clinical scales (PANSS, NSA-16, BPRS, ICG, GAF, Ham A, Ham D, Psychosis Severity Dimensions).
2. Patient reported outcomes: POMS, visual analogue scales
3. Plasma homocysteine value

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Clinica Universidad De Navarra

Sponsor organisation

Clinica Universidad De Navarra

Address

Avenue Pio XII 36

City

Pamplona

Postcode

31008

Country

Spain

Scientific contact point

Organisation

Clinica Universidad De Navarra

Contact name

Patricio Molero Santos

Public contact point

Organisation

Clinica Universidad De Navarra

Contact name

UCEC

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications