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Pharmacogenetics of Metformin Action in PCOS

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ClinicalTrials.gov Identifier: NCT00703508
Recruitment Status : Completed
First Posted : June 23, 2008
Results First Posted : April 25, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Virginia Commonwealth University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Polycystic Ovary Syndrome
Intervention Drug: Metformin 500 mg tablet
Enrollment 55
Recruitment Details  
Pre-assignment Details 55 subjects were enrolled, however some subjects failed to meet eligibility criteria resulting in 26 subjects initiating and completing all study phases.
Arm/Group Title Metformin
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Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration

Metformin 500 mg tablet: Metformin 500 mg tablets; two tablets every 12 hours for 9 months

Period Title: Overall Study
Started 26
Completed 26
Not Completed 0
Arm/Group Title Metformin
Hide Arm/Group Description

Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration

Metformin 500 mg tablet: Metformin 500 mg tablets; two tablets every 12 hours for 9 months

Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
27.9  (4.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
26
 100.0%
Male
0
   0.0%
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 26 participants
35.0  (7.6)
1.Primary Outcome
Title Number of Responders/Non-responders for Each STK11 rs8111699 Genotype (C/G, C/C, G/G)
Hide Description Responders were defined as those that had a doubling of baseline ovulation rate estimated by self-report of menstrual history.
Time Frame 9 months
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title G/G Genotype C/G Genotype C/C Genotype
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Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Overall Number of Participants Analyzed 26 26 26
Measure Type: Number
Unit of Measure: participants
responders 6 7 5
non-responders 3 4 1
2.Primary Outcome
Title Ovulation Rate Over Study Duration for STK11 Genotypes CC, CG and GG
Hide Description Ovulations were determined by measurement of daily urine pregnanediol-3-glucuronide or weekly progesterone levels over 6-9 months of study duration for each participant. The ovulation rate was calculated as the number of confirmed ovulation events per months of study participation.
Time Frame 9 months
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title G/G Genotype C/G Genotype C/C Genotype
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Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Overall Number of Participants Analyzed 9 11 6
Mean (Standard Deviation)
Unit of Measure: ovulations/month
0.47  (0.310) 0.36  (0.396) 0.34  (0.336)
3.Secondary Outcome
Title Determine in Which Genotype(s) Frequency of Ovulation Correlates With Improvement in Reduction in Total Testosterone and Insulin Sensitivity as Measured by the Matsuda Index.
Hide Description Bivariate fit (RSquare with P values) of ovulation rate post treatment by change in total testosterone and Matsuda Index for each of the 3 genotypes (G/G, C/G, C/C)
Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Individuals that were lost to follow up had missing data on testosterone and OGTT (oral glucose tolerance testing) for Matsuda index.
Arm/Group Title G/G Genotype C/G Genotype C/C Genotype
Hide Arm/Group Description:
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Overall Number of Participants Analyzed 9 7 3
Measure Type: Number
Unit of Measure: Correlation coefficient (r^2)
Ovulation rate vs Testosterone post treatment 0.138956 0.035449 0.049263
Ovulation rate vs Matsuda Index post treatment 0.27144 0.01918 0.132059
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G/G Genotype
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0234
Comments Ovulation rate vs Testosterone post-treatment, threshold for statistical significance = p<0.05
Method Regression, Linear
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C/G Genotype
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0740
Comments Ovulation rate vs Testosterone post-treatment, threshold for statistical significance = p<0.05
Method Regression, Linear
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection C/C Genotype
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4698
Comments Ovulation rate vs Testosterone post-treatment, threshold for statistical significance = p<0.05
Method Regression, Linear
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection G/G Genotype
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1180
Comments Ovulation rate vs Matsuda Index post-treatment, threshold for statistical significance = p < 0.05.
Method Regression, Linear
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection C/G Genotype
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0311
Comments Ovulation rate vs Matsuda Index post-treatment, threshold for statistical significance = p < 0.05.
Method Regression, Linear
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection C/C Genotype
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1586
Comments Ovulation rate vs Matsuda Index post-treatment, threshold for statistical significance = p < 0.05.
Method Regression, Linear
Comments [Not Specified]
Time Frame For entire 9 months of study plus 30 days after study completion
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Metformin
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Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration

Metformin 500 mg tablet: Metformin 500 mg tablets; two tablets every 12 hours for 9 months

All-Cause Mortality
Metformin
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Metformin
Affected / at Risk (%) # Events
Total   0/26 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Metformin
Affected / at Risk (%) # Events
Total   1/26 (3.85%)    
Blood and lymphatic system disorders   
Anemia   1/26 (3.85%)  1
Indicates events were collected by systematic assessment
Interpretations of our findings are limited by our small sample size.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Kai Cheang
Organization: Virginia Commonwealth University
Phone: (804) 828-2257
Publications of Results:
Cheang KI, Bhavi Modi, Maria Shulleeta, William S. Evans, Lubna Pal, Jerome F. Strauss and John E. Nestler: Genetic Polymorphisms and Ovulatory Responsiveness to Metformin in Women with Polycystic Ovary Syndrome. Endo Reviews 36 (2): Supplement THR-109, Apr. 2015.
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00703508     History of Changes
Other Study ID Numbers: HM11153
2U54HD034449 ( U.S. NIH Grant/Contract )
First Submitted: June 20, 2008
First Posted: June 23, 2008
Results First Submitted: January 5, 2017
Results First Posted: April 25, 2017
Last Update Posted: June 14, 2017