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Oral Contraceptives in the Metabolic Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00205504
First received: September 13, 2005
Last updated: May 24, 2013
Last verified: May 2013
History of Changes
  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 4

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:

U.S. FDA Resources

Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Changes in Insulin Sensitivity Associated With Oral Contraceptive (OC) Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Insulin sensitivity was assessed by frequent sampling intravenous glucose tolerance test (FSIVGTT).


Secondary Outcome Measures:
  • Changes in Lipid Profile Compared Associated With OC Use Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    The lipid profile is assessed through blood sample analysis for low-density lipoprotein (LDL), Triglycerides and high-density lipoprotein (HDL).

  • Inflammatory Marker Changes, High Sensitive C-reactive Protein (Hs-CRP) and Adiponectin, Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Inflammatory markers are assessed through blood analysis for C-reactive protein (hs-CRP) and adiponectin.

  • Changes in Estrogen Metabolites (Plasma) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
  • Changes in Waist-to-Hip Ratio Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    Waist-to-hip ratio is assessed through calculated ratio of waist and hip circumference.

  • Inflammatory Marker Changes (MCP-1) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Inflammatory marker is assessed through blood analysis for Monocyte chemotactic protein-1 (MCP-1).

  • Changes in Blood Pressure Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Changes in Body Mass Index (BMI) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    Body Mass Index is a calculation of height and weight: kg/m²

  • Changes in Waist Circumference Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
  • Inflammatory Marker Changes, Soluble Vascular Cell Adhesion Molecule (sVCAM) and Soluble Intercellular Adhesion Molecule (sICAM), Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    These inflammatory markers are assessed through blood analysis of Soluble Vascular Cell Adhesion Molecule (sVCAM) and soluble intercellular adhesion molecule (sICAM).


Enrollment: 36
Study Start Date: June 2005
Estimated Study Completion Date: June 2014
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:

  1. Acceptable health based on interview, medical history, physical examination, and laboratory tests (comprehensive metabolic panel - SMA20, and complete blood count - CBC);
  2. Have not taken oral contraceptives (OCs) in the past 3 months;
  3. Ability to comply with the requirements of the study;

  4. 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 high-density lipoprotein (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 Body Mass Index (BMI) > 30 kg/m2 and lean women should have a Body Mass Index BMI < 25 kg/m2.

Exclusion Criteria:

  1. Diabetes mellitus by fasting glucose or a 2-hour oral glucose tolerance test (OGTT);
  2. 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);
  3. History of thromboembolism, myocardial infarction, cerebrovascular accident, vascular disease, known coagulopathy, prolonged immobilization, or recent major surgery (within past 6 months);
  4. Systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg (mild hypertension is not an exclusion criterion);
  5. History of breast cancer, migraine headaches, or age ≥ 35 years and smoker of ≥ 20 cigarettes/day;
  6. Use of metformin, thiazolidinediones, anti-hyperlipidemic drugs, anti-hypertensive drugs, glucocorticoids, or anti-androgens (spironolactone, flutamide, etc.) within 3 months;
  7. Documented or suspected illicit drug abuse or alcoholism within one year;
  8. Ingestion of any investigational drugs within 3 months prior to the study onset; and
  9. Pregnancy or lactation (≤ 6 weeks postpartum);
  10. 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

Publications:

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00205504     History of Changes
Other Study ID Numbers: AD Williams
Study First Received: September 13, 2005
Results First Received: January 25, 2012
Last Updated: May 24, 2013
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 June 18, 2013