Clinical trial NCT02205437: Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia
Official title: Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia: Evidence From Pharmacogenetics in the Light of Personalized Medicine
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Schizophrenia
Keywords: Schizophrenia
Psychosis
Antipsychotics
Treatment response
Metabolic side effects
Gene expression
RNA
Genes
Lead sponsor: Fundación Marques de Valdecilla
Sponsor class: OTHER
Collaborators: name: Centro de Investigación Biomédica en Red de Salud Mental
name: Instituto de Investigación Marqués de Valdecilla
First posted: 2014-07-31
Enrollment: 200
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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).

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.


Eligibility criteria: Inclusion Criteria:

* Patients followed up for 3 years in the First Episode Psychosis Clinical Program (PAFIP).
* 15-60 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Clinical improvement.
timeFrame: 1 year.
Secondary outcomes:
measure: Changes in metabolic parameters.
timeFrame: 1 year.
measure: Effect of gender and cannabis use in the profile of gene expression associated with schizophrenia.
timeFrame: 1 year.
Other outcomes:
Locations:
city: Santander
country: Spain
facility: University Hospital Marques de Valdecilla
state: Cantabria
Study officials:
affiliation: 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
name: Benedicto Crespo-Facorro, Professor
role: PRINCIPAL_INVESTIGATOR
References: