Impact of Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use

April 16, 2018 updated by: Priscila Akemi Yamamoto, São Paulo State University

Impact of Genetic Polymorphisms of OCT2 and OCTN1 on the Kinetic Disposition of Gabapentin in Patients Undergoing Chronic Use of the Drug

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • Araraquara, São Paulo, Brazil, 14800903
        • Universidade Estadual Paulista Julio de Mesquita Filho

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with 18 years old or older, both gender.
  • Patients undergoing chronic use of gabapentin (at least one week).

Exclusion Criteria:

  • Pregnant and lactating patients.
  • Patients who were in use of OCT2 and OCTN1 inhibitors.
  • Patients who disagree to continue the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Homozygous for the wild type allele

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.
Procedure: Sparse blood sampling
Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.
Procedure: Urine sampling
Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).
Procedure: DNA extraction
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
Drug: Gabapentin
All patients undergoing chronic treatment with gabapentin are being recruited.
Other Names:
  • GAB
Active Comparator: Homo- or heterozygous for rare alleles

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.
Procedure: Sparse blood sampling
Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.
Procedure: Urine sampling
Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).
Procedure: DNA extraction
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
Drug: Gabapentin
All patients undergoing chronic treatment with gabapentin are being recruited.
Other Names:
  • GAB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gabapentin plasma concentration.
Time Frame: Up to 240 minutes after gabapentin administration.
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).
Up to 240 minutes after gabapentin administration.
OCT2 and OCTN1 genotyping
Time Frame: Up to 5 minutes before gabapentin administration
The single nucleotide polymorphisms of SLC22A2 gene (c.808G>T) and SLC22A4 (c.1507C>T) are being evaluated in all included patients.
Up to 5 minutes before gabapentin administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

São Paulo State University

Collaborators

University of Sao Paulo

Investigators

  • Principal Investigator: Fabíola D. Eckeli, Prof., University of Sao Paulo
  • Principal Investigator: Edgar Ianhez Júnior, Hospital Estadual de Américo Brasiliense
  • Study Chair: Natália V. de Moraes, Prof., Universidade Estadual Paulista Julio de Mesquita Filho

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

February 1, 2018

Study Completion (Actual)

February 1, 2018

Study Registration Dates

First Submitted

November 18, 2016

First Submitted That Met QC Criteria

November 25, 2016

First Posted (Estimate)

November 30, 2016

Study Record Updates

Last Update Posted (Actual)

April 18, 2018

Last Update Submitted That Met QC Criteria

April 16, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OCTGab

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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