Combination Metformin and Oral Contraception for Polycystic Ovary Syndrome (PCOS)

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00682890
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if adding Metformin, a drug that reduces insulin resistance, to birth control pills will reduce the risk of developing type 2 diabetes, high blood pressure. high lipid levels and heart disease in women with PCOS

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome; PCOS; Insulin Sensitivity	Drug: placebo; Drug: metformin	Phase 4

Detailed Description

Inclusion criteria: PCOS women between the ages of 18-45,< 8 periods annually, elevated serum free testosterone, normal thyroid function tests and serum prolactin, exclusion of late onset adrenal hyperplasia, acceptable health based on interview and medical history, physical exam and lab tests, ability to comply with the requirements of the study and to provide signed, witnessed informed consent.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Combination Metformin and Oral Contraception for Polycystic Ovary Syndrome (PCOS)
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Placebo tablet and birth control pill daily	Drug: placebo; placebo birth control pill daily
Active Comparator: 2 metformin 2000 mg and birth control pill daily	Drug: metformin; 2000 mg per day for 3 months daily birth control pill

Outcome Measures

Primary Outcome Measures

1. Change in Insulin Sensitivity Measures: Insulin Sensitivity Index (ISI) [baseline and 3 months]

   Insulin sensitivity as measured by a combination of insulin sensitivity index (ISI) which should go up after 3 month treatment period to show improvement, and insulin sensitivity (SI) which should go down after 3 month treatment period to show improvement. Note that the ISI as developed by Matsuda and DeFronzo from a calculation based on results from a standard oral glucose tolerance test (OGTT) (doi: 10.2337/diacare.22.9.1462 Diabetes Care September 1999 vol. 22 no. 9 1462-1470) is recorded as units on an arbitrary scale. SI data is based on a calculation derived from analysis of results of frequently sampled intravenous glucose tolerance test (FSIVGTT) by Bergman et al (doi:10.1172/JCI112886/J Clin Invest. 1987;79(3):790-800) and is reported with units min-1/(µlU/L).

2. Change in Insulin Sensitivity Measures: Insulin Sensitivity (SI) [baseline and 3 months]

   Insulin sensitivity as measured by a combination of insulin sensitivity index (ISI) which should go up after 3 month treatment period to show improvement, and insulin sensitivity (SI) which should go down after 3 month treatment period to show improvement. Note that the ISI as developed by Matsuda and DeFronzo from a calculation based on results from a standard oral glucose tolerance test (OGTT) (doi: 10.2337/diacare.22.9.1462 Diabetes Care September 1999 vol. 22 no. 9 1462-1470) is recorded as units on an arbitrary scale. SI data is based on a calculation derived from analysis of results of frequently sampled intravenous glucose tolerance test (FSIVGTT) by Bergman et al (doi:10.1172/JCI112886/J Clin Invest. 1987;79(3):790-800) and is reported with units min-1/(µlU/L).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ages 18-45, , 8 menstrual cycles annually, elevated serum free testosterone, normal thyroid function test and serum prolactin, exclusion of late onset adrenal hyperplasia

Exclusion Criteria:

• Diabetes mellitus, pulmonary, cardiac, renal, hepatic, cholestatic, neurologic, psychiatric, infectious, malignant diseases,history of breast cancer, history of Deep Vein Thrombosis, pregnancy and lactation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	General Clinical Research Center	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University

Investigators

• Study Director: Leo Dunn, MD, DSMB

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT00682890
• Other Study ID Numbers: R03HD047298
• First Posted: May 23, 2008
• Last Update Posted: Aug 20, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Insulin Resistance; Syndrome; Metformin

Study Results

Participant Flow

Recruitment Details	All recruitment and testing conducted at VCU General Clinical Research Center from August 2006 to December 2009
Pre-assignment Detail	Following enrollment but prior to group assignment 5 subject were excluded based on screening results. Randomized remaining 23 subjects.

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo tablet and birth control pill daily	metformin 2000 mg and birth control pill daily
Period Title: Overall Study
STARTED	12	11
COMPLETED	10	9
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Placebo	Metformin	Total
Arm/Group Description	Placebo tablet and birth control pill daily	metformin 2000 mg and birth control pill daily	Total of all reporting groups
Overall Participants	10	9	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (1.3)	26.6 (1.4)	25.5 (1.4)
Sex: Female, Male (Count of Participants)
Female	10 100%	9 100%	19 100%
Male	0 0%	0 0%	0 0%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	32.6 (2.3)	36.2 (2.5)	34.4 (2.4)

Outcome Measures

1. Primary Outcome

Title	Change in Insulin Sensitivity Measures: Insulin Sensitivity Index (ISI)
Description	Insulin sensitivity as measured by a combination of insulin sensitivity index (ISI) which should go up after 3 month treatment period to show improvement, and insulin sensitivity (SI) which should go down after 3 month treatment period to show improvement. Note that the ISI as developed by Matsuda and DeFronzo from a calculation based on results from a standard oral glucose tolerance test (OGTT) (doi: 10.2337/diacare.22.9.1462 Diabetes Care September 1999 vol. 22 no. 9 1462-1470) is recorded as units on an arbitrary scale. SI data is based on a calculation derived from analysis of results of frequently sampled intravenous glucose tolerance test (FSIVGTT) by Bergman et al (doi:10.1172/JCI112886/J Clin Invest. 1987;79(3):790-800) and is reported with units min-1/(µlU/L).
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo tablet and birth control pill daily	metformin 2000 mg and birth control pill daily
Measure Participants	10	9
ISI at baseline	4.7 (1.6)	7.3 (1.7)
ISI at month 3	4.4 (0.96)	5.9 (1.0)
ISI change vs baseline	-0.3 (1.1)	-1.4 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	P value on change at 3 months for placebo group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Change in Insulin Sensitivity Measures: Insulin Sensitivity (SI)
Description	Insulin sensitivity as measured by a combination of insulin sensitivity index (ISI) which should go up after 3 month treatment period to show improvement, and insulin sensitivity (SI) which should go down after 3 month treatment period to show improvement. Note that the ISI as developed by Matsuda and DeFronzo from a calculation based on results from a standard oral glucose tolerance test (OGTT) (doi: 10.2337/diacare.22.9.1462 Diabetes Care September 1999 vol. 22 no. 9 1462-1470) is recorded as units on an arbitrary scale. SI data is based on a calculation derived from analysis of results of frequently sampled intravenous glucose tolerance test (FSIVGTT) by Bergman et al (doi:10.1172/JCI112886/J Clin Invest. 1987;79(3):790-800) and is reported with units min-1/(µlU/L).
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Metformin
Arm/Group Description	Placebo tablet and birth control pill daily	metformin 2000 mg and birth control pill daily
Measure Participants	10	9
SI at baseline	2.26 (0.48)	3.83 (0.78)
SI at 3 months	2.8 (0.87)	2.11 (0.44)
SI change vs baseline	0.544 (0.79)	-1.72 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	3 months
Arm/Group Title	Placebo		Metformin
Arm/Group Description	Placebo tablet and birth control pill daily		metformin 2000 mg and birth control pill daily
All Cause Mortality
	Placebo		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)

Limitations/Caveats

study duration was relatively brief,earlier serum markers of the inflammatory process,e.g.,IL-6, were not evaluated,sample size planned was not achieved despite intensive recruitment efforts.

More Information

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.