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Effect of Genetic Variants in MATE1 and OCT3 on the Pharmacodynamics of Metformin in African Americans (#6113)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01681693
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, (hOCT3), and the multidrug and toxin extrusion transporter, MATE1 to test the hypothesis that genetic variation in hOCT3 and hMATE1 are associated with variation in the pharmacokinetics and/or pharmacodynamics of the antidiabetic agent, metformin.


Condition Intervention Phase
Healthy
Type 2 Diabetes Mellitus
 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 Variants in MATE1 and OCT3 Transporters on the Pharmacodynamics of Metformin in African Americans With Type II Diabetes Mellitus.

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 OCT3 and MATE1 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 OCT3 and MATE1 exhibit altered glucose lowering response to metformin.


Estimated Enrollment: 68
Study Start Date: February 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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:

To investigate the potential association of polymorphic genetic variants MATE1 and OCT3 with altered response to metformin, a genotype to phenotype strategy is employed. Specifically, the investigators will evaluate this hypothesis in African-Americans, a population which has a high incidence of type 2 diabetes and which has high variant allele frequencies (44.5% for MATE1-66T>C and 11.3% in OCT3-81G>delGA) relative to other ethic groups. To assess the effects of these variants on metformin response, the investigators will measure metformin renal clearance (pharmacokinetics of metformin), and plasma glucose and insulin levels (pharmacodynamic response) in healthy and diabetic patients who carry either the reference or variant alleles.

  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 African American
  • Subject status is healthy volunteer from t In the event that diabetes is indicated in a normal subject based on OGTT results, we will notify the patients' primary care physician. he SOPHIE cohort OR diagnosis of T2DM based on American Diabetes Association (ADA) criteria
  • Subjects over 18 years old and below 60 years
  • 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:

  • Unable to confirm African-American ethnicity
  • Under 18 years old
  • Pregnant or lactating women (female subjects will have a urine pregnancy test at the screening visit).
  • 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)
  • Risk of urinary or gastric retention or narrow-angle glaucoma (by medical history examination)
  • Impaired renal function (e.g as suggested by abnormal creatinine clearance, eGFR <60 or serum creatinine >1.4 mg/dl in females and >1.5 mg/dl in males) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction (heart attack), and septicemia, abnormal heart rhythms (tachyarrhythmias; heart beat > 100 beats per minute).
  • Impaired hepatic function (> 1.5 times the upper limit of normal)
  • Evidence of anemia (hemoglobin <10 g)
  • Taking a medication that could confound study results, such as known substrates or inhibitors of OCT3 and MATE1, such as cimetidine.
  • They do not provide consent to participate in the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681693

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: NCT01681693     History of Changes
Other Study ID Numbers: 6113
Study First Received: August 1, 2012
Last Updated: September 5, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013