Oral Contraceptives in the Metabolic Syndrome

NCT00205504 | Completed Phase 4 Results

• 1 other identifier: HM4060
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metabolic Syndrome X; Insulin Resistance; Obesity; Cardiovascular Diseases

Keywords

Inflammatory markers, oral contraceptions, obesity, metabolic syndrome X

Outcome Measures

Primary Outcomes (1)

• Changes in Insulin Sensitivity Associated With Oral Contraceptive (OC) Use Compared Among (1) Obese Women and (2) Lean Women

  Insulin sensitivity was assessed by frequent sampling intravenous glucose tolerance test (FSIVGTT).

  Baseline and 6 months

Secondary Outcomes (9)

• Changes in Lipid Profile Compared Associated With OC Use Among (1) Obese Women and (2) Lean Women

  Baseline and 6 months

• 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

  Baseline and 6 months

• Changes in Estrogen Metabolites (Plasma) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women

  Baseline and 6 months

• Changes in Waist-to-Hip Ratio Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women

  Baseline and 6 months

• Inflammatory Marker Changes (MCP-1) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women

  Baseline and 6 months

Study Arms (3)

Obese women with metabolic syndrome

ACTIVE COMPARATOR

Drug: Ortho Tri Cyclen

Obese women without metabolic syndrome

ACTIVE COMPARATOR

Drug: Ortho Tri Cyclen

lean women without metabolic syndrome

ACTIVE COMPARATOR

Drug: Ortho Tri Cyclen

Interventions

Ortho Tri Cyclen DRUG

Ortho Tri Cyclen, one tablet daily, for 6 cycles

Obese women with metabolic syndrome; Obese women without metabolic syndrome; lean women without metabolic syndrome

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Acceptable health based on interview, medical history, physical examination, and laboratory tests (comprehensive metabolic panel - SMA20, and complete blood count - CBC);
• Have not taken oral contraceptives (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:
• increased waist circumference \> 35 inches,
• hypertriglyceridemia ≥ 150 mg/dL,
• low high-density lipoprotein (HDL) cholesterol \< 50 mg/dL in women,
• hypertension (≥ 130/≥ 85 mmHg),
• 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.

You may not qualify if:

• 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);
• 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);

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University General Clinical Research Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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. doi: 10.1016/j.fertnstert.2011.05.039. Epub 2011 Jun 15.

  PMID: 21676394 RESULT

MeSH Terms

Conditions

Metabolic Syndrome; Insulin Resistance; Obesity; Cardiovascular Diseases

Interventions

Moxifloxacin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Kai Cheang, Principal Investigator
• Organization: Virginia Commonwealth University

kicheang@vcu.edu

804-828-9698

Study Officials

• Kai I Cheang, Pharm.D.

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

• John E Nestler, M.D.

  Virginia Commonwealth University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: June 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 8, 2018
• Results First Posted: May 7, 2012

Record last verified: 2018-07

Locations

US (1)