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

Phase 4

• Conditions: Vaginosis, Bacterial
• Interventions: Drug: Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring

• Registration Number: NCT01448291
• Lead Sponsor: Eastern Virginia Medical School

Brief Summary

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:

1. Determine biomarkers of inflammation, including defensins and cytokines, concentrations in women with normal vaginal flora (Nugent Score 0 - 3) before and after NuvaRing® use

2. Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration before and after treatment with NuvaRing®

3. Monitor for changes in the Nugent score before and after NuvaRing® use

4. Assess the antimicrobial activity of vaginal fluid before and after NuvaRing® use

5. 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

1. 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.

2. 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.

Study Timeline

• Study First Submitted: 2011-07-08
• Study Start: 2011-10
• Study First Submitted QC: 2011-10-06
• Study First Posted: 2011-10-07
• Status Verified: 2012-04
• Last Update Submitted: 2012-04-23
• Last Update Posted: 2012-04-24
• Primary Completion: 2012-10
• Study Completion: 2013-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. 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)
2. Women with a normal menstrual cycle (21-35 days) for the past three cycles
3. Women with normal pelvic anatomy (by physical exam)
4. Negative urine pregnancy test
5. Normal pap smear within the past 12 months

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Exclusion Criteria

1. Pregnancy
2. Current breastfeeding
3. Less than 6 weeks post partum
4. Current IUD or Implanon use
5. Depot Medroxyprogesterone Acetate use within the past 6 months
6. Current diagnosis of uterine infection
7. Use of hormonal contraception within the past 30 days
8. Current cervical dysplasia
9. Chronic immune suppression
10. Chronic use of immune suppressors such as steroids
11. Chronic antibiotic use
12. Diabetes or fasting blood glucose >105
13. Hysterectomy
14. Uncontrolled hypertension (systolic BP≥140/ diastolic BP≥ 90)
15. Migraine headaches complicated by aura or focal neurologic deficits
16. Menopause
17. Standard contraindications to combined oral contraceptive use (thrombophilia, active liver disease, active deep venous thrombosis, history of thrombosis)
18. Use of tobacco products ≥ 35 years of age
19. Two or more symptomatic genital herpes simplex virus (HSV) outbreaks in past 12 months
20. Human immunodeficiency virus
21. Vulvovaginal candidiasis
22. Trichamonas vaginalis
23. Neisseria gonorrhea
24. Chlamydia trachomatis
25. Bacterial vaginosis
26. Nugent scores of 4 or greater
27. Use of any other study medication within the past 30 days

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nuvaring	Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring	This is a single-group study in which data points after use of the etonogestrel/ethinyl estradiol vaginal ring will be compared to baseline.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration after 3 months of treatment with NuvaRing®	Baseline and 3 months

Trial Locations

Locations (1)

Clinical Research Center at Eastern Virginia Medical School; 🇺🇸 Norfolk, Virginia, United States