Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia

NCT02205437 | Unknown

• 1 other identifier: GEXANT
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is a severe and chronic mental disorder. The lifetime risk of schizophrenia is around 1%. Its course is chronic and frequently disabling. The keystone of schizophrenia treatment is antipsychotic medications. The use of antipsychotics represents a huge public health and economic burden to society. Most of antipsychotics drugs are "metoo" drugs, directly or indirectly replicating dopamine D2 receptor blockade. Pharmaceutical companies have aimed to produce drugs with a general indication for all patients with schizophrenia with a "one-size-fits-all" strategy with no targeting or stratification. Second generation antipsychotics partly improve positive symptoms and are quite often associated to weight gain, metabolic changes and increased risk of cardiovascular diseases. Antipsychotics only achieve a certain degree of clinical improvement in a percentage of patients (45%) and 30% of the patients are treatment resistant. In light of the current deadlock, there is an urgent need to expand the horizon of pharmacological research by elucidating new mechanisms related to antipsychotic actions. An alternative strategy is the comparison of gene expression profiles in drug-naive accurately ill patients before and after antipsychotic treatment has been initiated. Our research group has a great experience in the field and has been working on this hypothesis in the latest years. We propose a continuation project to thoroughly explore the clinical implications (clinical response to antipsychotic drugs or emergence of metabolic side effects) of the variants in gene expression we have recently described in schizophrenia patients. This project takes advantage of an exceptional (regarding to the detailed knowledge of clinical outcome and side effect profile) longitudinal cohort of drug-naive patients with schizophrenia who had been followed up for three years at the University Hospital Marqués de Valdecilla.

Conditions

Schizophrenia

Keywords

Schizophrenia; Psychosis; Antipsychotics; Treatment response; Metabolic side effects; Gene expression; RNA; Genes

Outcome Measures

Primary Outcomes (1)

• Clinical improvement.

  Changes in the total scores of the Scale for the Assessment of Positive Symptoms (SAPS) and Negative Symptoms (SANS), the Brief Psychiatric Rating Scale (BPRS) and the severity scale of the Clinical Global Impression (CGI) scale.

  1 year.

Secondary Outcomes (2)

• Changes in metabolic parameters.

  1 year.

• Effect of gender and cannabis use in the profile of gene expression associated with schizophrenia.

  1 year.

Study Arms (6)

Controls

Healthy subjects without psychotic disorder.

Drug-naive patients

Drug-naive (never medicated) schizophrenia patients.

Patients responder to treatment

Patients with a good clinical response to treatment (define by a marked improvement of positive symptoms) at 3 months and at 1 year.

Patients non-responder to treatment

Patients with a poor clinical response to treatment at 3 months and at 1 year.

Patients with metabolic side effects

Patients with metabolic side effects associated to treatment.

Patients with non-metabolic side effects

Patients with no metabolic side effects associated to treatment.

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Individuals included in the First Episode Psychosis Clinical Program (PAFIP) at the University Hospital Marqués de Valdecilla (Santander - Cantabria).

You may qualify if:

• Patients followed up for 3 years in the First Episode Psychosis Clinical Program (PAFIP).
• years.
• Living in the catchment area.
• Experiencing their first episode of psychosis.
• No prior treatment with antipsychotic medication or, if previously treated, a total life time of adequate antipsychotic treatment of less than 6 weeks.
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for brief psychotic disorder, schizophreniform disorder, schizophrenia, or schizoaffective disorder.

You may not qualify if:

• Meeting DSM-IV criteria for drug dependence.
• Meeting DSM-IV criteria for mental retardation.
• Having a history of neurological disease or head injury.

Sponsors & Collaborators

• Fundación Marques de Valdecilla: lead
• Centro de Investigación Biomédica en Red de Salud Mental: collaborator
• Instituto de Investigación Marqués de Valdecilla: collaborator

Study Sites (1)

University Hospital Marques de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, RNA

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Benedicto Crespo-Facorro, Professor

  University Hospital Marqués de Valdecilla, IDIVAL, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain. CIBERSAM Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benedicto Crespo-Facorro, Professor

CONTACT

+34 942202545; benedicto.crespo@unican.es

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: July 31, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 14, 2020

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)