Genetic Variation in OCT1 and Response to Metformin

This study has been withdrawn prior to enrollment.
(No funding)
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00588172
First received: December 22, 2007
Last updated: August 16, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: Metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Genetic Variation in OCT1 and Response to Metformin

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in glucose area under the curve after a mixed meal in response to metformin [ Time Frame: before and after 1 week of metformin ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in glucose disappearance and suppression of endogenous glucose production in response to metformin [ Time Frame: before and after 1 week of metformin therapy ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2010
Estimated Study Completion Date: June 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00588172

Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Adrian Vella, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Adrian Vella MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00588172     History of Changes
Other Study ID Numbers: 07-004310, OCT1 and metformin
Study First Received: December 22, 2007
Last Updated: August 16, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Metformin
Type 2 diabetes
Oct1

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

ClinicalTrials.gov processed this record on October 20, 2014