Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia (GEXANT)

Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia: Evidence From Pharmacogenetics in the Light of Personalized Medicine

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.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Spain
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • University Hospital Marqués de Valdecilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in metabolic parameters.	This parameters are Cholesterol, Triglycerides, Glucose and Homeostasis model assessment (HOMA) index.	1 year.
Effect of gender and cannabis use in the profile of gene expression associated with schizophrenia.		1 year.

Collaborators and Investigators

• Sponsor: Fundación Marques de Valdecilla
• Collaborators: Centro de Investigación Biomédica en Red de Salud Mental; Instituto de Investigación Marqués de Valdecilla

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: July 29, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (ESTIMATE): July 31, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Treatment response; Gene expression; Antipsychotics; RNA; Genes; Metabolic side effects
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: GEXANT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No