Effect of the Etonogestrel 0.12mg/Ethinyl Estradiol 0.015mg Vaginal Ring on Vaginal Innate and Inflammatory Biomarkers

Study Overview
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Brief Summary
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It is not known if the use of NuvaRing® alters these innate and inflammatory biomarkers of inflammation. Hypothesis: The hypothesis is that NuvaRing® will alter inflammatory biomarkers of inflammation, such as vaginal defensin and cytokine levels, resulting in an overall anti-inflammatory milieu in the vagina. Specific aims of this study are to: Determine biomarkers of inflammation, including defensins and cytokines, concentrations in women with normal vaginal flora (Nugent Score 0 - 3) before and after NuvaRing® use Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration before and after treatment with NuvaRing® Monitor for changes in the Nugent score before and after NuvaRing® use Assess the antimicrobial activity of vaginal fluid before and after NuvaRing® use Assess HIV infectivity ex vivo on biopsy specimens before and after NuvaRing® use Methods This is a prospective, open-label, nonrandomized study. Participants will serve as their own controls. The Clinical Research Center of Eastern Virginia Medical School, Norfolk, Virginia, U.S.A. will be the only study site.

Detailed Description
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To complete specific aim #1, the investigators will use commercially available elisa kits to measure human defensins, inflammatory cytokines, and anti-inflammatory cytokines in vaginal fluid washings collected before and after use of NuvaRing. To complete specific aim #2, the investigators will collect biopsies of the uterine cervix before and after NuvaRing use. Specimens will undergo histopathological measures for overall appearance, epithelial integrity, epithelial thickness, leukocyte infiltration, congestion, and edema. The investigators will quantitate the number of CD45+ and NFkB+ cells using immunohistology in the cervical epithelium.

Official Title
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The Effects of the Etonogestrel 0.12mg/Ethinyl Estradiol 0.015mg Vaginal Ring (NuvaRing®) on Vaginal Innate and Inflammatory Biomarkers

Conditions
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Vaginosis, Bacterial

Intervention / Treatment
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* Drug: Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women (age 18 - 45) interested in using NuvaRing® for contraception for 3 or more months, and women who are not at risk for pregnancy (i.e. abstinent, tubal sterilization, partner with vasectomy) Women with a normal menstrual cycle (21-35 days) for the past three cycles Women with normal pelvic anatomy (by physical exam) Negative urine pregnancy test Normal pap smear within the past 12 months Exclusion Criteria: Pregnancy Current breastfeeding Less than 6 weeks post partum Current IUD or Implanon use Depot Medroxyprogesterone Acetate use within the past 6 months Current diagnosis of uterine infection Use of hormonal contraception within the past 30 days Current cervical dysplasia Chronic immune suppression Chronic use of immune suppressors such as steroids Chronic antibiotic use Diabetes or fasting blood glucose >105 Hysterectomy Uncontrolled hypertension (systolic BP≥140/ diastolic BP≥ 90) Migraine headaches complicated by aura or focal neurologic deficits Menopause Standard contraindications to combined oral contraceptive use (thrombophilia, active liver disease, active deep venous thrombosis, history of thrombosis) Use of tobacco products ≥ 35 years of age Two or more symptomatic genital herpes simplex virus (HSV) outbreaks in past 12 months Human immunodeficiency virus Vulvovaginal candidiasis Trichamonas vaginalis Neisseria gonorrhea Chlamydia trachomatis Bacterial vaginosis Nugent scores of 4 or greater Use of any other study medication within the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nuvaring<br>This is a single-group study in which data points after use of the etonogestrel/ethinyl estradiol vaginal ring will be compared to baseline. | Drug: Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring<br>* Etonogestrel 0.12mg/Ethinyl Estradiol 0.015mg Vaginal Ring (NuvaRing®) for 3 months<br>* Other names: NuvaRing®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine biomarkers of inflammation, including defensins and cytokines, concentrations in women with normal vaginal flora (Nugent Score 0 - 3) after 3 months of NuvaRing® use |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration after 3 months of treatment with NuvaRing® |  | Baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contraception, Nuvaring, Vaginal inflammation, Bacterial vaginosis, Nugent score