<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02205437</url>
  </required_header>
  <id_info>
    <org_study_id>GEXANT</org_study_id>
    <nct_id>NCT02205437</nct_id>
  </id_info>
  <brief_title>Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia</brief_title>
  <acronym>GEXANT</acronym>
  <official_title>Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia: Evidence From Pharmacogenetics in the Light of Personalized Medicine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Marques de Valdecilla</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centro de Investigación Biomédica en Red de Salud Mental</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto de Investigación Marqués de Valdecilla</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundación Marques de Valdecilla</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Schizophrenia is a severe and chronic mental disorder. The lifetime risk of schizophrenia is&#xD;
      around 1%. Its course is chronic and frequently disabling. The keystone of schizophrenia&#xD;
      treatment is antipsychotic medications. The use of antipsychotics represents a huge public&#xD;
      health and economic burden to society. Most of antipsychotics drugs are &quot;metoo&quot; drugs,&#xD;
      directly or indirectly replicating dopamine D2 receptor blockade. Pharmaceutical companies&#xD;
      have aimed to produce drugs with a general indication for all patients with schizophrenia&#xD;
      with a &quot;one-size-fits-all&quot; strategy with no targeting or stratification. Second generation&#xD;
      antipsychotics partly improve positive symptoms and are quite often associated to weight&#xD;
      gain, metabolic changes and increased risk of cardiovascular diseases. Antipsychotics only&#xD;
      achieve a certain degree of clinical improvement in a percentage of patients (45%) and 30% of&#xD;
      the patients are treatment resistant. In light of the current deadlock, there is an urgent&#xD;
      need to expand the horizon of pharmacological research by elucidating new mechanisms related&#xD;
      to antipsychotic actions. An alternative strategy is the comparison of gene expression&#xD;
      profiles in drug-naive accurately ill patients before and after antipsychotic treatment has&#xD;
      been initiated. Our research group has a great experience in the field and has been working&#xD;
      on this hypothesis in the latest years. We propose a continuation project to thoroughly&#xD;
      explore the clinical implications (clinical response to antipsychotic drugs or emergence of&#xD;
      metabolic side effects) of the variants in gene expression we have recently described in&#xD;
      schizophrenia patients. This project takes advantage of an exceptional (regarding to the&#xD;
      detailed knowledge of clinical outcome and side effect profile) longitudinal cohort of&#xD;
      drug-naive patients with schizophrenia who had been followed up for three years at the&#xD;
      University Hospital Marqués de Valdecilla.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical improvement.</measure>
    <time_frame>1 year.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in metabolic parameters.</measure>
    <time_frame>1 year.</time_frame>
    <description>This parameters are Cholesterol, Triglycerides, Glucose and Homeostasis model assessment (HOMA) index.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of gender and cannabis use in the profile of gene expression associated with schizophrenia.</measure>
    <time_frame>1 year.</time_frame>
  </secondary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Healthy subjects without psychotic disorder.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug-naive patients</arm_group_label>
    <description>Drug-naive (never medicated) schizophrenia patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients responder to treatment</arm_group_label>
    <description>Patients with a good clinical response to treatment (define by a marked improvement of positive symptoms) at 3 months and at 1 year.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients non-responder to treatment</arm_group_label>
    <description>Patients with a poor clinical response to treatment at 3 months and at 1 year.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with metabolic side effects</arm_group_label>
    <description>Patients with metabolic side effects associated to treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with non-metabolic side effects</arm_group_label>
    <description>Patients with no metabolic side effects associated to treatment.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood, RNA&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals included in the First Episode Psychosis Clinical Program (PAFIP) at the&#xD;
        University Hospital Marqués de Valdecilla (Santander - Cantabria).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients followed up for 3 years in the First Episode Psychosis Clinical Program&#xD;
             (PAFIP).&#xD;
&#xD;
          -  15-60 years.&#xD;
&#xD;
          -  Living in the catchment area.&#xD;
&#xD;
          -  Experiencing their first episode of psychosis.&#xD;
&#xD;
          -  No prior treatment with antipsychotic medication or, if previously treated, a total&#xD;
             life time of adequate antipsychotic treatment of less than 6 weeks.&#xD;
&#xD;
          -  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)&#xD;
             criteria for brief psychotic disorder, schizophreniform disorder, schizophrenia, or&#xD;
             schizoaffective disorder.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Meeting DSM-IV criteria for drug dependence.&#xD;
&#xD;
          -  Meeting DSM-IV criteria for mental retardation.&#xD;
&#xD;
          -  Having a history of neurological disease or head injury.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benedicto Crespo-Facorro, Professor</last_name>
    <role>Principal Investigator</role>
    <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</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Benedicto Crespo-Facorro, Professor</last_name>
    <phone>+34 942202545</phone>
    <email>benedicto.crespo@unican.es</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital Marques de Valdecilla</name>
      <address>
        <city>Santander</city>
        <state>Cantabria</state>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>January 13, 2020</last_update_submitted>
  <last_update_submitted_qc>January 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fundación Marques de Valdecilla</investigator_affiliation>
    <investigator_full_name>Benedicto Crespo-Facorro</investigator_full_name>
    <investigator_title>Associate Professor of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Psychosis</keyword>
  <keyword>Antipsychotics</keyword>
  <keyword>Treatment response</keyword>
  <keyword>Metabolic side effects</keyword>
  <keyword>Gene expression</keyword>
  <keyword>RNA</keyword>
  <keyword>Genes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02205437
org study id: GEXANT
nct id: NCT02205437
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Clinical improvement.
time frame: 1 year.
description: 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.
measure: Changes in metabolic parameters.
time frame: 1 year.
description: This parameters are Cholesterol, Triglycerides, Glucose and Homeostasis model assessment (HOMA) index.
measure: Effect of gender and cannabis use in the profile of gene expression associated with schizophrenia.
time frame: 1 year.
arm group label: Controls
description: Healthy subjects without psychotic disorder.
arm group label: Drug-naive patients
description: Drug-naive (never medicated) schizophrenia patients.
arm group label: Patients responder to treatment
description: Patients with a good clinical response to treatment (define by a marked improvement of positive symptoms) at 3 months and at 1 year.
arm group label: Patients non-responder to treatment
description: Patients with a poor clinical response to treatment at 3 months and at 1 year.
arm group label: Patients with metabolic side effects
description: Patients with metabolic side effects associated to treatment.
arm group label: Patients with non-metabolic side effects
description: Patients with no metabolic side effects associated to treatment.
Whole blood, RNA
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 15 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Benedicto Crespo-Facorro, Professor
role: Principal Investigator
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
last name: Benedicto Crespo-Facorro, Professor
phone: +34 942202545
email: benedicto.crespo@unican.es
facility: 
status: Recruiting
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Fundación Marques de Valdecilla
investigator full name: Benedicto Crespo-Facorro
investigator title: Associate Professor of Psychiatry
mesh term: Schizophrenia
sharing ipd: No