Genetic Variation in OCT1 and Response to Metformin

August 16, 2010 updated by: Mayo Clinic
Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished. Moreover a polymorphism with a 20% minor allele frequency in Caucasians also alters the effect of metformin on glucose tolerance (the net result of glucose uptake and glucose release) after ingestion of 75g of glucose. However, it is unknown if this polymorphism affects suppression of endogenous glucose production or stimulation of peripheral glucose uptake by metformin, or both, and to what degree. We propose to utilize established methodology to measure glucose turnover in response to a mixed meal to determine how common genetic variation in OCT1 alters response to metformin in healthy volunteers. This will clarify the effect of these variants on response to metformin in humans. The knowledge gained from this study will help to design future studies examining the role of OCT1 genotype in determining initial therapy for type 2 diabetes.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion criteria: -

  1. Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function.
  2. Age 18 - 40.
  3. Willingness to participate in this study.

Exclusion criteria: -

  1. Fasting glucose > 100mg/dL on one occasion.
  2. Use of medication other than stable thyroid hormone replacement or oral contraception.
  3. Subjects must not be pregnant or < 6 months postpartum at the time of study.
  4. Prior abdominal surgery other than hysterectomy, appendectomy or tubal ligation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: 1
Individuals with no nsSNPs or mutations known to alter oct1 function
Drug: Metformin
1000mg bid for 1 week
Active Comparator: 2
Individuals with nsSNPs or mutations known to alter oct1 function
Drug: Metformin
1000mg bid for 1 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in glucose area under the curve after a mixed meal in response to metformin
Time Frame: before and after 1 week of metformin
before and after 1 week of metformin

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in glucose disappearance and suppression of endogenous glucose production in response to metformin
Time Frame: before and after 1 week of metformin therapy
before and after 1 week of metformin therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

June 1, 2010

Study Completion (Anticipated)

June 1, 2011

Study Registration Dates

First Submitted

December 22, 2007

First Submitted That Met QC Criteria

December 22, 2007

First Posted (Estimate)

January 8, 2008

Study Record Updates

Last Update Posted (Estimate)

August 17, 2010

Last Update Submitted That Met QC Criteria

August 16, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-004310
  • OCT1 and metformin

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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