<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/NCT02977208</url>
  </required_header>
  <id_info>
    <org_study_id>OCTGab</org_study_id>
    <nct_id>NCT02977208</nct_id>
  </id_info>
  <brief_title>Impact of Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use</brief_title>
  <official_title>Impact of Genetic Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use of the Drug</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>São Paulo State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>São Paulo State University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the influence of genetic polymorphisms of OCTN1 and OCT2 and&#xD;
      other possible covariates on the kinetic disposition of GAB in patients undergoing GAB&#xD;
      chronic treatment. Thus, patients treated with GAB, for at least one week, are being&#xD;
      investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gabapentin (GAB), an anticonvulsant used for the treatment of epilepsy and chronic pain, has&#xD;
      nonlinear kinetics, it is not metabolized and it is mainly eliminated by renal excretion.&#xD;
      Studies suggest that the renal excretion of GAB is dependent on active secretion by organic&#xD;
      cation transporter 2 (OCT2) and organic cation/ergothioneine transporter 1 (OCTN1). These&#xD;
      transporters are expressed at the membrane of the renal proximal tubules and they are&#xD;
      involved in the elimination of endogenous compounds and many drugs. The genetic polymorphism&#xD;
      of drug transporters has been studied to explain the kinetic disposition variability of their&#xD;
      substrates. The objective of this study is to investigate the influence of genetic&#xD;
      polymorphisms of OCTN1 and OCT2 and other possible covariates (e.g., sex, age, creatinine&#xD;
      clearance, body mass index) on the kinetic disposition of GAB in patients undergoing GAB&#xD;
      chronic treatment. Patients treated with GAB, for at least one week, are being investigated.&#xD;
      Blood and urine samples are being collected to GAB pharmacokinetic analysis, serum creatinine&#xD;
      analysis and for genotyping. The plasma concentration of GAB will be assessed using liquid&#xD;
      chromatography with UV detection (LC-UV).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2016</start_date>
  <completion_date type="Actual">February 2018</completion_date>
  <primary_completion_date type="Actual">February 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gabapentin plasma concentration.</measure>
    <time_frame>Up to 240 minutes after gabapentin administration.</time_frame>
    <description>Blood samples will be collected at 0, 90 and 240 minutes after gabapentin administration. The gabapentin plasma concentration will be assessed using liquid chromatography with UV detection (LC-UV).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>OCT2 and OCTN1 genotyping</measure>
    <time_frame>Up to 5 minutes before gabapentin administration</time_frame>
    <description>The single nucleotide polymorphisms of SLC22A2 gene (c.808G&gt;T) and SLC22A4 (c.1507C&gt;T) are being evaluated in all included patients.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Epilepsy</condition>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Homozygous for the wild type allele</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with 18 years old or older with epilepsy, neuropathic pain or any chronic pain undergoing chronic treatment with gabapentin are being recruited.&#xD;
Sparse blood sampling are being collected up to 4 h after administration of the drug for pharmacokinetic study. Urine sampling are being collected during the dosing interval, only in patients hospitalized at the Hospital Estadual de Américo Brasiliense (HEAB). Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G&gt;T and SLC22A4 c.1507C&gt;T polymorphisms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Homo- or heterozygous for rare alleles</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with 18 years old or older with epilepsy, neuropathic pain or any chronic pain undergoing chronic treatment with gabapentin are being recruited.&#xD;
Sparse blood sampling are being collected up to 4 h after administration of the drug for pharmacokinetic study. Urine sampling are being collected during the dosing interval, only in patients hospitalized at the Hospital Estadual de Américo Brasiliense (HEAB). Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G&gt;T and SLC22A4 c.1507C&gt;T polymorphisms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sparse blood sampling</intervention_name>
    <description>Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.</description>
    <arm_group_label>Homo- or heterozygous for rare alleles</arm_group_label>
    <arm_group_label>Homozygous for the wild type allele</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Urine sampling</intervention_name>
    <description>Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).</description>
    <arm_group_label>Homo- or heterozygous for rare alleles</arm_group_label>
    <arm_group_label>Homozygous for the wild type allele</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>DNA extraction</intervention_name>
    <description>Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G&gt;T and SLC22A4 c.1507C&gt;T polymorphisms</description>
    <arm_group_label>Homo- or heterozygous for rare alleles</arm_group_label>
    <arm_group_label>Homozygous for the wild type allele</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gabapentin</intervention_name>
    <description>All patients undergoing chronic treatment with gabapentin are being recruited.</description>
    <arm_group_label>Homo- or heterozygous for rare alleles</arm_group_label>
    <arm_group_label>Homozygous for the wild type allele</arm_group_label>
    <other_name>GAB</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with 18 years old or older, both gender.&#xD;
&#xD;
          -  Patients undergoing chronic use of gabapentin (at least one week).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and lactating patients.&#xD;
&#xD;
          -  Patients who were in use of OCT2 and OCTN1 inhibitors.&#xD;
&#xD;
          -  Patients who disagree to continue the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fabíola D. Eckeli, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sao Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Edgar Ianhez Júnior</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Estadual de Américo Brasiliense</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Natália V. de Moraes, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Estadual Paulista Júlio de Mesquita Filho</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidade Estadual Paulista Júlio de Mesquita Filho</name>
      <address>
        <city>Araraquara</city>
        <state>São Paulo</state>
        <zip>14800903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 25, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>April 16, 2018</last_update_submitted>
  <last_update_submitted_qc>April 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>São Paulo State University</investigator_affiliation>
    <investigator_full_name>Priscila Akemi Yamamoto</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Gabapentin</keyword>
  <keyword>OCT2</keyword>
  <keyword>OCTN1</keyword>
  <keyword>Pharmacogenetics</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Polymorphisms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
  </intervention_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/NCT02977208
org study id: OCTGab
nct id: NCT02977208
lead sponsor: 
collaborator: 
has dmc: No
This study aims to evaluate the influence of genetic polymorphisms of OCTN1 and OCT2 and
      other possible covariates on the kinetic disposition of GAB in patients undergoing GAB
      chronic treatment. Thus, patients treated with GAB, for at least one week, are being
      investigated.
Gabapentin (GAB), an anticonvulsant used for the treatment of epilepsy and chronic pain, has
      nonlinear kinetics, it is not metabolized and it is mainly eliminated by renal excretion.
      Studies suggest that the renal excretion of GAB is dependent on active secretion by organic
      cation transporter 2 (OCT2) and organic cation/ergothioneine transporter 1 (OCTN1). These
      transporters are expressed at the membrane of the renal proximal tubules and they are
      involved in the elimination of endogenous compounds and many drugs. The genetic polymorphism
      of drug transporters has been studied to explain the kinetic disposition variability of their
      substrates. The objective of this study is to investigate the influence of genetic
      polymorphisms of OCTN1 and OCT2 and other possible covariates (e.g., sex, age, creatinine
      clearance, body mass index) on the kinetic disposition of GAB in patients undergoing GAB
      chronic treatment. Patients treated with GAB, for at least one week, are being investigated.
      Blood and urine samples are being collected to GAB pharmacokinetic analysis, serum creatinine
      analysis and for genotyping. The plasma concentration of GAB will be assessed using liquid
      chromatography with UV detection (LC-UV).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Gabapentin plasma concentration.
time frame: Up to 240 minutes after gabapentin administration.
description: Blood samples will be collected at 0, 90 and 240 minutes after gabapentin administration. The gabapentin plasma concentration will be assessed using liquid chromatography with UV detection (LC-UV).
measure: OCT2 and OCTN1 genotyping
time frame: Up to 5 minutes before gabapentin administration
description: The single nucleotide polymorphisms of SLC22A2 gene (c.808G>T) and SLC22A4 (c.1507C>T) are being evaluated in all included patients.
arm group label: Homozygous for the wild type allele
arm group type: Active Comparator
description: Patients with 18 years old or older with epilepsy, neuropathic pain or any chronic pain undergoing chronic treatment with gabapentin are being recruited.
Sparse blood sampling are being collected up to 4 h after administration of the drug for pharmacokinetic study. Urine sampling are being collected during the dosing interval, only in patients hospitalized at the Hospital Estadual de Américo Brasiliense (HEAB). Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms.
arm group label: Homo- or heterozygous for rare alleles
arm group type: Active Comparator
description: Patients with 18 years old or older with epilepsy, neuropathic pain or any chronic pain undergoing chronic treatment with gabapentin are being recruited.
Sparse blood sampling are being collected up to 4 h after administration of the drug for pharmacokinetic study. Urine sampling are being collected during the dosing interval, only in patients hospitalized at the Hospital Estadual de Américo Brasiliense (HEAB). Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms.
intervention type: Procedure
intervention name: Sparse blood sampling
description: Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.
arm group label: Homo- or heterozygous for rare alleles
arm group label: Homozygous for the wild type allele
intervention type: Procedure
intervention name: Urine sampling
description: Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).
arm group label: Homo- or heterozygous for rare alleles
arm group label: Homozygous for the wild type allele
intervention type: Procedure
intervention name: DNA extraction
description: Blood sample are being collected for DNA extraction. DNA are being extracted from the whole blood of all patients for genotyping of the SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms
arm group label: Homo- or heterozygous for rare alleles
arm group label: Homozygous for the wild type allele
intervention type: Drug
intervention name: Gabapentin
description: All patients undergoing chronic treatment with gabapentin are being recruited.
arm group label: Homo- or heterozygous for rare alleles
arm group label: Homozygous for the wild type allele
other name: GAB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Fabíola D. Eckeli, Prof.
role: Principal Investigator
affiliation: University of Sao Paulo
last name: Edgar Ianhez Júnior
role: Principal Investigator
affiliation: Hospital Estadual de Américo Brasiliense
last name: Natália V. de Moraes, Prof.
role: Study Chair
affiliation: Universidade Estadual Paulista Júlio de Mesquita Filho
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: São Paulo State University
investigator full name: Priscila Akemi Yamamoto
investigator title: Principal investigator
mesh term: Chronic Pain
mesh term: Gabapentin
sharing ipd: No