Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
Information provided by (Responsible Party):
University of California, San Francisco Identifier:
First received: August 1, 2012
Last updated: October 21, 2014
Last verified: October 2014
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
Type 2 Diabetes Mellitus
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: 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:

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 ]
    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 ]
    To test whether individuals with genetic variants of transporters OCT3 and MATE1 exhibit altered glucose lowering response to metformin.

Enrollment: 33
Study Start Date: February 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (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.

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01681693

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

Responsible Party: University of California, San Francisco Identifier: NCT01681693     History of Changes
Other Study ID Numbers: 6113
Study First Received: August 1, 2012
Last Updated: October 21, 2014

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on April 28, 2017