Obesity and Oral Contraceptive Failure

This study is currently recruiting participants.
Verified September 2013 by Oregon Health and Science University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ganesh Cherala, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT01944306
First received: September 10, 2013
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

Contraceptive failure is the primary cause of unintended pregnancy in the United States. With obesity rates at epidemic proportions, any association between obesity and strategies that prevent undesired pregnancies constitutes a significant public health and economic concern. Evidence from recent epidemiological studies and our preliminary data (sub-therapeutic levels of steroid hormones due to drug clearance and half-life) suggest that obesity reduces oral contraceptive efficacy. Furthermore, preliminary analysis suggested that a sub-group of obese women, defined by their own birth weight, are at higher risk of contraceptive failure. Further studies are necessary to investigate whether birth weight, a surrogate marker of in utero growth restriction, is a useful diagnostic marker for the identification of women prone to contraceptive failure. Such an understanding is critical to finding a contraceptive strategy with better efficacy for these women.

The overall goal of this project is to test pharmacokinetics of oral contraceptive agents in obese women with low birth weight and compare to obese women with normal birth weight. The main hypothesis for this proposal is that an adverse in utero environment programs the expression and function of enzymes and transporters that underlie pharmacokinetics of oral contraceptives, and leads to contraceptive failure.

Reproductive-aged, ovulatory women of obese BMI >30 kg/m2 with normal birth weight (5.5-8 lbs; n=10) and low birth weight (<5.5 lbs; n=10), will be placed on oral contraceptives for 1 month. At several key time points, synthetic steroid pharmacokinetics, gonadotropins (luteinizing hormone, follicle-stimulating hormone) and ovarian hormone levels (estradiol, progesterone) will be monitored.


Condition
Contraception
Fetal Growth Retardation
Infant, Small for Gestational Age
Obesity

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prenatal Growth Programs Oral Contraceptive Metabolism and Effectiveness

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Measure pharmacokinetic parameters of oral contraceptives including drug clearance. [ Time Frame: on day 21 of oral contraceptive use ] [ Designated as safety issue: No ]
    Serum concentration-time data for each subject will be analyzed using a non-compartmental model assumption. Serum concentrations below the lower limit of quantitation (LLOQ) at the beginning and end of the profile will be set to zero. Serum concentration-time profiles will be summarized using descriptive statistics and graphical display. Student t-tests will be used to test whether the average values of each of the pharmacokinetic parameters, including free concentrations, differ between the four groups of women.


Secondary Outcome Measures:
  • Measure levels of gonadotropins and ovarian hormones [ Time Frame: Days 21-25 of oral contraceptive use ] [ Designated as safety issue: No ]
    To compare gonadotopin levels, average leutinizing hormone and follicle stimulating hormone levels measured for days 21-25 will be calculated. In addition, the follicle stimulating hormone/leutinizing hormone ratio will be calculated at each time point. The average levels of these measures will then be compared between the four groups of women using a student's t-test.


Biospecimen Retention:   Samples With DNA

Blood, Plasma, and Urine will be collected for the analaysis of drug levels and genotyping of various genes that could explain pharmacokinetics of oral contraceptives.


Estimated Enrollment: 40
Study Start Date: August 2013
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Low birth-weight, obese
Low birth-weight, normal body weight
Normal birth-weight, obese
Normal birth-weight, normal body weight

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Reproductive-aged, ovulatory women seeking to initiate contraception with combined oral contraceptives will be recruited from the female population of the Portland, OR area. Subjects must have access to their birth weight record. Enrollment will be confined to women who have not used a hormonal contraceptive method for 30 days or more prior to enrollment.

Criteria

Inclusion Criteria:

  • age 18 to 35.
  • single progesterone level of 3 ng/mL or greater during the luteal phase (days 18 to 25) in the menstrual cycle prior to dosing with oral contraceptives.

Exclusion Criteria:

  • absolute/relative contraindications to ethinyl estradiol and levonorgestrel.
  • impaired liver function.
  • history of deep venous thrombosis.
  • hypertension (> 140/90).
  • diabetes with vascular changes.
  • migraines with aura or neurological changes.
  • history of myocardial infarction, pulmonary embolus, stroke or breast cancer.
  • anemia (hematocrit < 36%).
  • actively seeking or involved in a weight loss program (must be weight stable)
  • pregnancy, breastfeeding, or seeking pregnancy.
  • diagnosis of Polycystic Ovarian Syndrome.
  • recent (4 week) use of hormonal contraceptives (patch or ring included), intrauterine, or implantable hormonal contraception.
  • DepoProvera use within six months.
  • current use of drugs that interfere with metabolism of sex steroids.
  • smokers.
  • uncontrolled thyroid dysfunction.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01944306

Contacts
Contact: Ganesh Cherala, PhD 503-418-0447 cheralag@ohsu.edu
Contact: Jacob Pearson, BS 503-494-5014 pearson@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Ganesh Cherala, PhD    503-418-0447    cheralag@ohsu.edu   
Contact: Jacob Pearson, BS    503-494-5014    pearson@ohsu.edu   
Principal Investigator: Ganesh Cherala, PhD         
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Ganesh Cherala, PhD Oregon Health and Science University
  More Information

Publications:
Responsible Party: Ganesh Cherala, Assistant Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01944306     History of Changes
Other Study ID Numbers: IRB00009569, 2K12HD043488-11
Study First Received: September 10, 2013
Last Updated: September 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
Pharmacokinetics
Pharmacology, Clinical
Drug Efficacy
Drug Failure
Contraceptive Agents

Additional relevant MeSH terms:
Nutrition Disorders
Fetal Growth Retardation
Obesity
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes
Overnutrition
Overweight
Body Weight
Signs and Symptoms
Contraceptive Agents
Contraceptives, Oral
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on April 17, 2014