Oral Contraceptives in the Metabolic Syndrome - Full Text View

Sponsor:	Virginia Commonwealth University
Information provided by (Responsible Party):	Virginia Commonwealth University
ClinicalTrials.gov Identifier:	NCT00205504

Purpose

Oral contraceptives (OCs) are the most widely used method of reversible birth control. However, the long-term cardiovascular safety of the widely used low-dose OCs (ethinyl-estradiol < 50 mcg) is still debated. Although cardiovascular events are rare in young women whether they use OCs or not, the risks of myocardial infarction and ischemic stroke are increased among users of OCs who have conventional cardiovascular risk factors such as use of tobacco, diabetes or hypercholesterolemia. However, the risk of cardiovascular events in OC users with emerging cardiovascular risk factors (such as obesity and the metabolic syndrome) have not been investigated. Recently, the metabolic syndrome has been linked with the risk of cardiovascular disease. The syndrome is a clustering of risk factors in a single individual, and its underlying cause may be insulin resistance. Whether the metabolic syndrome predicts a higher cardiovascular risk in OC users has not been studied. This is a critical problem because the metabolic syndrome is prevalent in 24% of adults. Until the cardiovascular risks in users of OC are clearly defined, the appropriate use of OC with the least harm would not be possible.

The investigator's long-term goal is to understand the best way to prevent and treat cardiovascular disease in women. The objective of this particular project is to obtain pilot data on the extent to which the metabolic syndrome and obesity affects glucose metabolism and cardiovascular risks in women taking OCs. The researchers hypothesize that women with metabolic syndrome and obese women will have worsened glucose metabolism and elevated cardiovascular risks associated with OC use, when compared to normal weight women without the metabolic syndrome. Results of this study will clarify the risk factors for cardiovascular events in women taking OCs, and will serve as pilot data for a National Institutes of Health (NIH) proposal. Once the cardiovascular risk factors of OC users are understood, clinicians can make better informed decisions about contraceptive choices for their patients.

Condition	Intervention	Phase
Metabolic Syndrome X Insulin Resistance Obesity Cardiovascular Diseases	Drug: Ortho Tri Cyclen	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Oral Contraceptives in the Metabolic Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Metabolic Syndrome Obesity

Drug Information available for: Moxifloxacin Moxifloxacin hydrochloride

U.S. FDA Resources

Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:

Difference in insulin sensitivity changes associated with oral contraceptive use compared among (1)obese women with the metabolic syndrome, (2) obese women without the metabolic syndrome, and (3) lean women without the metabolic syndrome [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Changes in lipid profile, blood pressure, weight, waist-hip ratio and other anthropometric measures associated with OC use among (2)obese women with and (2) without metabolic syndrome, and (3) lean women without metabolic syndrome [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Inflammatory and insulin sensitivity marker changes (CRP,PAI-1,tPA,adiponectin,VCAM,ICAM,RBP4,Fetuin-A and others) associated with OC use compared among (1)obese women with and(2)without metabolic syndrome, and(3)lean women without metabolic syndrome [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Changes in Estrogen metabolites associated with OC use [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	June 2005
Estimated Study Completion Date:	June 2012
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Obese women with metabolic syndrome	Drug: Ortho Tri Cyclen Ortho Tri Cyclen, one tablet daily, for 6 cycles
Active Comparator: Obese women without metabolic syndrome	Drug: Ortho Tri Cyclen Ortho Tri Cyclen, one tablet daily, for 6 cycles
Active Comparator: lean women without metabolic syndrome	Drug: Ortho Tri Cyclen Ortho Tri Cyclen, one tablet daily, for 6 cycles

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Acceptable health based on interview, medical history, physical examination, and laboratory tests (SMA20 and CBC);
Have not taken OCs in the past 3 months;
Ability to comply with the requirements of the study;
Ability and willingness to provide signed, witnessed informed consent. In addition, women with the metabolic syndrome must meet the National Cholesterol Education Program (NCEP) defined criteria of the metabolic syndrome, that is, having at least 3 of the 5 factors:
1. increased waist circumference > 35 inches,
2. hypertriglyceridemia ≥ 150 mg/dL,
3. low HDL cholesterol < 50 mg/dL in women,
4. hypertension (≥ 130/≥ 85 mmHg),
5. fasting glucose ≥ 100 mg/dL.

Obese women with or without the metabolic syndrome should have a BMI > 30 kg/m2 and lean women should have a BMI < 25 kg/m2.

Exclusion Criteria:

Diabetes mellitus by fasting glucose or a 2-hour oral glucose tolerance test (OGTT);
Clinically significant pulmonary, cardiac (including but not limited to ischemic heart disease, stable/unstable angina, and congestive heart failure), renal, hepatic, cholestatic, neurologic, psychiatric, infectious, and malignant disease (other than melanoma skin cancer);
History of thromboembolism, myocardial infarction, cerebrovascular accident, vascular disease, known coagulopathy, prolonged immobilization, or recent major surgery (within past 6 months);
Systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg (mild hypertension is not an exclusion criterion);
History of breast cancer, migraine headaches, or age ≥ 35 years and smoker of ≥ 20 cigarettes/day;
Use of metformin, thiazolidinediones, anti-hyperlipidemic drugs, anti-hypertensive drugs, glucocorticoids, or anti-androgens (spironolactone, flutamide, etc.) within 3 months;
Documented or suspected illicit drug abuse or alcoholism within one year;
Ingestion of any investigational drugs within 3 months prior to the study onset; and
Pregnancy or lactation (≤ 6 weeks postpartum);
Hematocrit < 33g/dL. These exclusion criteria are based on study requirements and also go beyond guidelines for OC use published by the World Health Organization.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00205504

Locations

United States, Virginia
Virginia Commonwealth University General Clinical Research Center
Richmond, Virginia, United States, 23298

Sponsors and Collaborators

Virginia Commonwealth University

Investigators

Principal Investigator:	Kai I Cheang, Pharm.D.	Virginia Commonwealth University
Study Director:	John E Nestler, M.D.	Virginia Commonwealth University

More Information

No publications provided by Virginia Commonwealth University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cheang KI, Essah PA, Sharma S, Wickham EP 3rd, Nestler JE. Divergent effects of a combined hormonal oral contraceptive on insulin sensitivity in lean versus obese women. Fertil Steril. 2011 Aug;96(2):353-359.e1. Epub 2011 Jun 15.

Responsible Party:	Virginia Commonwealth University
ClinicalTrials.gov Identifier:	NCT00205504 History of Changes
Other Study ID Numbers:	AD Williams
Study First Received:	September 13, 2005
Last Updated:	November 14, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:

Inflammatory markers, oral contraceptions, obesity, metabolic syndrome X

Additional relevant MeSH terms:

Cardiovascular Diseases
Insulin Resistance
Obesity
Metabolic Syndrome X
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

Contraceptive Agents
Norgestimate, ethinyl estradiol drug combination
Contraceptives, Oral
Moxifloxacin
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Anti-Infective Agents
Contraceptives, Oral, Combined

ClinicalTrials.gov processed this record on February 09, 2012