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

NCT ID: NCT01448291

Last Updated: 2012-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2013-03-31

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:

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

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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.

Conditions

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Vaginosis, Bacterial

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring

Intervention Type DRUG

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

Interventions

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Etonogestrel /Ethinyl Estradiol Contraceptive Vaginal Ring

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

Intervention Type DRUG

Other Intervention Names

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NuvaRing®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Eastern Virginia Medical School

OTHER

Sponsor Role lead

Responsible Party

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Thomas Kimble

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas D Kimble, MD

Role: PRINCIPAL_INVESTIGATOR

Eastern Virginia Medical School/CONRAD

Locations

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Clinical Research Center at Eastern Virginia Medical School

Norfolk, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Julia Caul

Role: CONTACT

7574465808

Facility Contacts

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Julia Caul

Role: primary

757-446-5808

References

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Iqbal SM, Kaul R. Mucosal innate immunity as a determinant of HIV susceptibility. Am J Reprod Immunol. 2008 Jan;59(1):44-54. doi: 10.1111/j.1600-0897.2007.00563.x.

Reference Type BACKGROUND
PMID: 18154595 (View on PubMed)

Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol. 2002 Sep;187(3):561-8. doi: 10.1067/mob.2002.125280.

Reference Type BACKGROUND
PMID: 12237628 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18635180 (View on PubMed)

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. doi: 10.1086/497168. Epub 2005 Oct 13.

Reference Type BACKGROUND
PMID: 16235171 (View on PubMed)

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. doi: 10.1136/sti.2007.026625. Epub 2007 Oct 2.

Reference Type BACKGROUND
PMID: 17911138 (View on PubMed)

Other Identifiers

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11-01-FB-0003

Identifier Type: OTHER

Identifier Source: secondary_id

CRC-NVR11

Identifier Type: -

Identifier Source: org_study_id

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