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

NCT ID: NCT02977208

Last Updated: 2018-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2018-02-28

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Epilepsy Chronic Pain

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Sparse blood sampling

Intervention Type PROCEDURE

Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.

Urine sampling

Intervention Type PROCEDURE

Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).

DNA extraction

Intervention Type PROCEDURE

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

Gabapentin

Intervention Type DRUG

All patients undergoing chronic treatment with gabapentin are being recruited.

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.

Group Type ACTIVE_COMPARATOR

Sparse blood sampling

Intervention Type PROCEDURE

Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.

Urine sampling

Intervention Type PROCEDURE

Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).

DNA extraction

Intervention Type PROCEDURE

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

Gabapentin

Intervention Type DRUG

All patients undergoing chronic treatment with gabapentin are being recruited.

Interventions

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Sparse blood sampling

Blood samples are being collected at times 0, 90 and 240 minutes after gabapentin administration.

Intervention Type PROCEDURE

Urine sampling

Urine samples are being collected during the dosing interval, only in patients hospitalized at Hospital Estadual de Américo Brasiliense (HEAB).

Intervention Type 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

Intervention Type PROCEDURE

Gabapentin

All patients undergoing chronic treatment with gabapentin are being recruited.

Intervention Type DRUG

Other Intervention Names

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GAB

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Sao Paulo

OTHER

Sponsor Role collaborator

São Paulo State University

OTHER

Sponsor Role lead

Responsible Party

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Priscila Akemi Yamamoto

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fabíola D. Eckeli, Prof.

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo

Edgar Ianhez Júnior

Role: PRINCIPAL_INVESTIGATOR

Hospital Estadual de Américo Brasiliense

Natália V. de Moraes, Prof.

Role: STUDY_CHAIR

Universidade Estadual Paulista Júlio de Mesquita Filho

Locations

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Universidade Estadual Paulista Júlio de Mesquita Filho

Araraquara, São Paulo, Brazil

Site Status

Countries

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Brazil

Other Identifiers

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OCTGab

Identifier Type: -

Identifier Source: org_study_id

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