Effect of Genetic Variants in MATE1 and OCT3 on the Pharmacodynamics of Metformin in African Americans

NCT01681693 | Completed Phase 1 DMC

• 1 other identifier: 6113
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Renal Clearance of the Metformin

  To test whether individuals with genetic variants of transporters OCT3 and MATE1 exhibit altered pharmacokinetics of metformin.

  24 hours post-dose

• Plasma glucose

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

  0, 15, 30, 45, 60, 90, 120, 180 minutes after glucose administration

Study Arms (1)

Metformin

EXPERIMENTAL

Subjects will be given an oral dose of metformin once per day for two days.

Drug: Metformin

Interventions

Metformin DRUG

Subjects will be given an oral dose of metformin once per day for two days.

Also known as: GLUCOPHAGE

Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Kathleen M Giacomini, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: September 10, 2012
• Study Start: February 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: October 23, 2014

Record last verified: 2014-10

Locations

US (1)