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Effect of Genetic Variation in the Transporter OCT2, MATE1 and MATE2-K on the PKPD of Metformin (#6112)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01681680
First received: August 1, 2012
Last updated: September 5, 2012
Last verified: September 2012
History of Changes
  Purpose

The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. The investigators will study individuals with particular genotypes of the human organic cation transporter, (hOCT2), and the multidrug and toxin extrusion transporters, MATE1, MATE2-K to test the hypothesis that genetic variation in hOCT2, hMATEE1 and hMATE2-K are associated with variation in the pharmacokinetics and/or pharmacodynamics of the antidiabetic agent, metformin.


Condition Intervention Phase
Healthy
 Drug: Metformin
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effect of Genetic Variation in the Transporter OCT2, MATE1 and MATE2-K on the Pharmacokinetics and Pharmacodynamics of Metformin

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Renal clearance of the Metformin [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
    To test whether individuals with genetic variants of transporters, OCT2, MATE1, and MATE2-K, exhibit altered pharmacokinetics of metformin.

  • Plasma glucose [ Time Frame: 0, 15, 30, 45, 60, 90, 120, 180 minutes after glucose administration ] [ Designated as safety issue: No ]
    To test whether individuals with genetic variants of transporters OCT2, MATE1, and MATE2-K, exhibit altered glucose lowering response to metformin.


Estimated Enrollment: 60
Study Start Date: October 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Metformin
Subjects will be given an oral dose of metformin once per day for two days.
 Drug: Metformin
Subjects will be given an oral dose of metformin once per day for two days.
Other Name: GLUCOPHAGE

Detailed Description:

In the proposed study, a genotype to phenotype strategy is employed to study the role of the transporters, OCT2, MATE1, and MATE2-K and related variants in response and disposition to a known substrate, metformin. Recently, one polymorphic variant in MATE1 (PMT4302, g.-66T>C) showed decreased promoter activity by 40-45% (p<0.01), and one MATE2-K variant (PMT5597, g.-130G>A) showed increased promoter activity by 30% (p<0.05), compared to the reference. Both are the most common promoter variants in each gene (the frequencies of PMT4302: 32.1% and 23.1% in Caucasian and Asian; PMT5597: 26.2% and 48.5% in Caucasian and Asian) (unpublished data, Giacomini group). Specifically, the investigators will measure renal clearance of metformin, and plasma glucose and insulin levels, in healthy Caucasian and Asian subjects who carry either the reference or variant alleles in order to evaluate the effects of these variants on metformin disposition and response.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects self-identify racial background, identify themselves, parents and four grandparents as Caucasian and or Chinese.
  • Subject status is healthy volunteer from the SOPHIE cohort
  • Subjects over 18 years old
  • Subjects who are healthy on the basis of medical history, physical examinations and laboratory tests if healthy volunteer from SOPHIE
  • Subjects who agree with the written informed consent to participate in the study.

Exclusion Criteria:

  • Under 18 years old
  • Pregnant or lactating woman (female subjects will have a urine pregnancy test at the Day 1 visit)
  • They report a prior history of any allergic reaction to metformin
  • Has a risk of congestive heart failure requiring pharmacologic treatment (medical history)
  • Has a prior history of renal* or hepatic dysfunction (renal and hepatic function will be evaluated based on screening blood tests conducted prior to study enrollment)
  • Anemic (screening lab values, hemoglobin <10 g)
  • Taking a medication that could confound study results (such as known substrates or inhibitors of OCT2, MATE1 and MATE2-K such as cimetidine)
  • Subjects are undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function
  • They do not consent to participate in the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681680

Locations
United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Kathleen M Giacomini, PhD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01681680     History of Changes
Other Study ID Numbers: 6112
Study First Received: August 1, 2012
Last Updated: September 5, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013