Clinical trial NCT02416154: Expression of IFN-epsilon in the Female Reproductive Tract
Official title: IFN-epsilon and Hormonal Contraceptive Modulation of the Risk of HIV Acquisition, Part 1: Expression in the Female Reproductive Tract
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Interferon Expression in the Female Reproductive Tract
Keywords: interferon-epsilon
female reproductive tract
neopterin
menstrual cycle
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: MIMR-PHI Institute, Australia
First posted: 2015-04-14
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy females aged18 through 35 years (inclusive) at screening

Brief summary: The proposed study aims to determine the expression of Interferon-ε (IFNε) in the female genital tract, which has never been mapped before in humans. High expression in other mammalian female reproductive tract (FRT) has been suggested to be important in anti-sexually transmitted infection (STI)/HIV immunity and its expression decreases with progestogen treatment. Future studies are planned to understand if hormonal contraceptives affect the presence of interferon in the healthy female genital tract, potentially changing the risk of for STI and HIV.

Detailed description: Objectives:

1. To optimize measurement protocols for IFNε and related biomarkers in samples from the female reproductive tract.
2. To quantify and characterize IFNε expression in the upper and lower genital tract and blood in normally cycling women during the follicular and luteal phases of the menstrual cycle.

Study design: This is a single site, parallel cross-sectional study

Specific Aims:

The aim of this study is to determine which "IFNε -related assays" can be performed on different types of FRT samples. The possible "IFNε-related assays" are:

* IFNε messenger ribonucleic acid (mRNA) levels by quantitative reverse transcriptase polymerase chain reaction (qRT PCR) (requiring frozen tissue processed for RNA)
* IFN Regulated Gene expression by qRT PCR, microarray or targeted gene set using Fluidigm platform (frozen tissue)
* PR and ER gene expression (as above)
* IFNε tissue protein levels\* (by immunoassay) and progesterone and estrogen receptors (PR/ER) by Western blotting (frozen tissue)
* IFNε and Neopterin (a well characterized compound whose production can be stimulated by IFNs and whose specificity in this setting needs validation) or other IFNε-biomarkers\*\* by immunoassay in cervicovaginal lavage (CVL) fluids
* Immunohistochemistry of IFNε, PR/ER, + other (e.g. cells, cytokines) (fixed tissue)

  * Studies of FRT samples from wild type and IFNε-/- mice would be used to first validate Neopterin as a "biomarker" of IFNε activity in the FRT; and microarray analyses may reveal other secreted proteins that may be used as "biomarkers" of IFNε activity.

Eligibility criteria: Inclusion Criteria:

1. Age 18 through 35 years (inclusive) at screening
2. Non-pregnant women in general good health as determined by the site clinician
3. Premenopausal with history of regular menstrual cycles (regular cycles defined as occurring every 21-35 days when not using hormones and with a variation of typical cycle length of no more than 5 days)
4. Regular and consistent condom use, prior surgical sterilization by participant or sexual partner, or heterosexually abstinent since last menses prior to enrollment
5. Able and willing to provide written informed consent to be screened for and to take part in the study, including willingness to undergo all study-related assessments and follow all study-related procedures
6. Able and willing to provide adequate locator information
7. HIV-uninfected based on testing performed by study staff at enrollment

Exclusion Criteria:

1. Use of any hormonal or intrauterine contraceptive method within 30 days of enrollment
2. Use of depot medroxyprogesterone acetate (DMPA) within 10 months of enrollment
3. Pregnancy or breastfeeding within 60 days of enrollment
4. Surgical procedure involving the pelvis in the 30 days prior to enrollment (includes dilation and curettage, cryosurgery and biopsy of the vagina, vulva, cervix, and endometrium)
5. Internal vaginal use of any device (includes sex toys, cervical caps, diaphragms, menstrual collection devices, and pessaries; excludes tampons and condoms) or product (includes spermicide, microbicide, douche, antifungal, steroid, or hormone) in the 30 days prior to enrolment (includes investigational products and devices)
6. New sexual partner within 90 days of enrollment
7. Urogenital infection or suspected infection within 30 days of enrollment including: symptomatic candidiasis, trichomonas vaginalis, and symptomatic bacterial vaginosis; or cervical infection, including N. gonorrhoea (GC), C. trachomatis (CT), or mucopurulent cervicitis; syphilis; herpes simplex virus (HSV) lesions, or other sores (Note: seropositive HSV without active lesions will not be excluded); acute pelvic inflammatory disease; urinary tract infection; recent exposure to a partner with GC, CT, Trichomonas, syphilis, or non-gonococcal urethritis (NGU)
8. Any history of immunosuppression (includes diabetes, HIV infection, and chronic steroid use or other immunosuppressive medications)
9. Antibiotic or antifungal therapy (vaginal or systemic) within 30 days of enrollment
10. Menses or other vaginal bleeding at the time of enrollment\* (\*Women who have vaginal bleeding at the scheduled enrollment visit may return at a different date to be re-examined and possibly enrolled provided they are still within the 90-day screening window and meet all criteria).
11. Vaginal or anal intercourse within 36 hours prior to enrollment
12. Heterosexual intercourse since last menses that places the participant at risk of pregnancy (without condom use or sterilization of at least one partner)
13. History of hysterectomy
14. History of malignancy within the pelvis (includes uterus, cervix, vagina, and vulva)
15. Any condition that, in the opinion of the Investigator, would preclude provision of consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Primary outcomes:
measure: Interferon epsilon expression
timeFrame: baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Center for Family Planning Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Hudson Institute of Medical Research
name: Paul Hertzog, PhD
role: PRINCIPAL_INVESTIGATOR
References: