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

Vaginosis, Bacterial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01448291
• Other study ID #: CRC-NVR11
• Secondary ID: 11-01-FB-0003
• Status: Recruiting
• Phase: Phase 4
• First received: July 8, 2011
• Last updated: April 23, 2012
• Start date: October 2011
• Est. completion date: March 2013

Study information

• Verified date: April 2012
• Source: Eastern Virginia Medical School
• Contact: Julia Caul
• Phone: 7574465808
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Vaginosis, Bacterial

Intervention

Drug:
• Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring
Etonogestrel 0.12mg/Ethinyl Estradiol 0.015mg Vaginal Ring (NuvaRing®) for 3 months

Locations

Country	Name	City	State
United States	Clinical Research Center at Eastern Virginia Medical School	Norfolk	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Virginia Medical School	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

Iqbal SM, Kaul R. Mucosal innate immunity as a determinant of HIV susceptibility. Am J Reprod Immunol. 2008 Jan;59(1):44-54. Review. — View Citation

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. — View Citation

Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol. 2002 Sep;187(3):561-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Determine changes in the integrity of cervicovaginal epithelium and leukocytic concentration after 3 months of treatment with NuvaRing®		Baseline and 3 months	Yes