Genetic Variation in OCT1 and Response to Metformin
Primary Purpose
Type 2 Diabetes
Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional basic science trial for Type 2 Diabetes focused on measuring Metformin, Type 2 diabetes, Oct1
Eligibility Criteria
Inclusion criteria: -
- 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.
- Age 18 - 40.
- Willingness to participate in this study.
Exclusion criteria: -
- Fasting glucose > 100mg/dL on one occasion.
- Use of medication other than stable thyroid hormone replacement or oral contraception.
- Subjects must not be pregnant or < 6 months postpartum at the time of study.
- Prior abdominal surgery other than hysterectomy, appendectomy or tubal ligation.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Active Comparator
Arm Label
1
2
Arm Description
Individuals with no nsSNPs or mutations known to alter oct1 function
Individuals with nsSNPs or mutations known to alter oct1 function
Outcomes
Primary Outcome Measures
Change in glucose area under the curve after a mixed meal in response to metformin
Secondary Outcome Measures
Change in glucose disappearance and suppression of endogenous glucose production in response to metformin
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00588172
Brief Title
Genetic Variation in OCT1 and Response to Metformin
Official Title
Genetic Variation in OCT1 and Response to Metformin
Study Type
Interventional
2. Study Status
Record Verification Date
August 2010
Overall Recruitment Status
Withdrawn
Why Stopped
No funding
Study Start Date
June 2010 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Mayo Clinic
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
Metformin, Type 2 diabetes, Oct1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Sham Comparator
Arm Description
Individuals with no nsSNPs or mutations known to alter oct1 function
Arm Title
2
Arm Type
Active Comparator
Arm Description
Individuals with nsSNPs or mutations known to alter oct1 function
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
1000mg bid for 1 week
Primary Outcome Measure Information:
Title
Change in glucose area under the curve after a mixed meal in response to metformin
Time Frame
before and after 1 week of metformin
Secondary Outcome Measure Information:
Title
Change in glucose disappearance and suppression of endogenous glucose production in response to metformin
Time Frame
before and after 1 week of metformin therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria: -
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.
Age 18 - 40.
Willingness to participate in this study.
Exclusion criteria: -
Fasting glucose > 100mg/dL on one occasion.
Use of medication other than stable thyroid hormone replacement or oral contraception.
Subjects must not be pregnant or < 6 months postpartum at the time of study.
Prior abdominal surgery other than hysterectomy, appendectomy or tubal ligation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Vella, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
12. IPD Sharing Statement
Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Genetic Variation in OCT1 and Response to Metformin
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