Effect of the Etonogestrel 0.12mg/Ethinyl Estradiol 0.015mg Vaginal Ring on Vaginal Innate and Inflammatory Biomarkers
Study Details
Study Description
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:
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Determine biomarkers of inflammation, including defensins and cytokines, concentrations in women with normal vaginal flora (Nugent Score 0 - 3) before and after NuvaRing® use
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Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration before and after treatment with NuvaRing®
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Monitor for changes in the Nugent score before and after NuvaRing® use
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Assess the antimicrobial activity of vaginal fluid before and after NuvaRing® use
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Nuvaring 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
Etonogestrel 0.12mg/Ethinyl Estradiol 0.015mg Vaginal Ring (NuvaRing®) for 3 months
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration after 3 months of treatment with NuvaRing® [Baseline and 3 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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Women with a normal menstrual cycle (21-35 days) for the past three cycles
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Women with normal pelvic anatomy (by physical exam)
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Negative urine pregnancy test
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Normal pap smear within the past 12 months
Exclusion Criteria:
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Pregnancy
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Current breastfeeding
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Less than 6 weeks post partum
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Current IUD or Implanon use
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Depot Medroxyprogesterone Acetate use within the past 6 months
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Current diagnosis of uterine infection
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Use of hormonal contraception within the past 30 days
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Current cervical dysplasia
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Chronic immune suppression
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Chronic use of immune suppressors such as steroids
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Chronic antibiotic use
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Diabetes or fasting blood glucose >105
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Hysterectomy
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Uncontrolled hypertension (systolic BP≥140/ diastolic BP≥ 90)
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Migraine headaches complicated by aura or focal neurologic deficits
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Menopause
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Standard contraindications to combined oral contraceptive use (thrombophilia, active liver disease, active deep venous thrombosis, history of thrombosis)
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Use of tobacco products ≥ 35 years of age
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Two or more symptomatic genital herpes simplex virus (HSV) outbreaks in past 12 months
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Human immunodeficiency virus
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Vulvovaginal candidiasis
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Trichamonas vaginalis
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Neisseria gonorrhea
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Chlamydia trachomatis
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Bacterial vaginosis
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Nugent scores of 4 or greater
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Use of any other study medication within the past 30 days
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Research Center at Eastern Virginia Medical School | Norfolk | Virginia | United States | 23507 |
Sponsors and Collaborators
- Eastern Virginia Medical School
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Thomas D Kimble, MD, Eastern Virginia Medical School/CONRAD
Study Documents (Full-Text)
None provided.More Information
Publications
- Cherpes TL, Marrazzo JM, Cosentino LA, Meyn LA, Murray PJ, Hillier SL. Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect. 2008 Feb;84(1):57-61. Epub 2007 Oct 2.
- Fan SR, Liu XP, Liao QP. Human defensins and cytokines in vaginal lavage fluid of women with bacterial vaginosis. Int J Gynaecol Obstet. 2008 Oct;103(1):50-4. doi: 10.1016/j.ijgo.2008.05.020. Epub 2008 Jul 16.
- Iqbal SM, Kaul R. Mucosal innate immunity as a determinant of HIV susceptibility. Am J Reprod Immunol. 2008 Jan;59(1):44-54. Review.
- John M, Keller MJ, Fam EH, Cheshenko N, Hogarty K, Kasowitz A, Wallenstein S, Carlucci MJ, Tuyama AC, Lu W, Klotman ME, Lehrer RI, Herold BC. Cervicovaginal secretions contribute to innate resistance to herpes simplex virus infection. J Infect Dis. 2005 Nov 15;192(10):1731-40. Epub 2005 Oct 13.
- Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol. 2002 Sep;187(3):561-8.
- CRC-NVR11
- 11-01-FB-0003