Quantification of Immune Cells in Women Using Contraception (CHIC II)

Study Overview
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Brief Summary
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This study is being done to understand if using birth control causes changes in the immune cells within the reproductive tract (including the cervix and the lining of the uterus) of healthy women. Immune cells are important because they help prevent infections from starting and help fight infections that have started. Immune cells are also the type of cells that HIV (human immunodeficiency virus) infects so understanding more about them will help to better understand how to prevent the spread of HIV. Immune cells will be studied from the reproductive tract of women who want to start using one of the following contraceptives: an oral contraceptive pill (COC), Depo-Provera (DMPA), the levonorgestrel IUD (Mirena®), the copper IUD (ParaGard®), or the etonogestrel subdermal implant (Nexplanon®).Immune cells will also be studied from the reproductive tract of women who are not using birth control and who are not at risk of pregnancy for comparison.

Official Title
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Quantification of Immune Cells in Women Using Contraception

Conditions
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HIV, Immune Cells (Mucosal and Systemic), Contraception

Intervention / Treatment
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* Drug: levonorgestrel exposure
* Drug: DMPA exposure
* Drug: etonogestrel exposure
* Device: IUD insertion
* Device: subdermal contraceptive implant insertion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 through 34 years (inclusive) at screening Non-pregnant women in general good health as determined by the site clinician 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) Women enrolling into the control group only: Regular and consistent condom use, prior surgical sterilization by participant or sexual partner, or heterosexually abstinent for entire study participation 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 Able and willing to provide adequate locator information HIV-uninfected based on testing performed by study staff at screening (per HIV testing algorithm in Appendices I) At screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products while enrolled in this trial Exclusion Criteria: Use of any hormonal or intrauterine contraceptive method within 30 days of enrollment Use of DMPA within 10 months of enrollment Pregnancy or breastfeeding within 60 days of enrollment 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) Internal vaginal use of any device (includes sex toys, cervical caps, diaphragms, menstrual collection devices, and pessaries; excludes tampons and condoms) or product (includes N9, microbicide, douche, antifungal, steroid, or hormone) in the 30 days prior to enrollment New sexual partner within 90 days of enrollment Urogenital infection or suspected infection within 30 days of enrollment including: symptomatic candidiasis, trichomonas vaginalis, and symptomatic bacterial vaginosis; or cervical infection, including N. gonorrhea, C. trachomatis, or mucopurulent cervicitis; syphilis; 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 NGU Any history of immunosuppression (includes diabetes, HIV infection, and chronic steroid use) Antibiotic or antifungal therapy (vaginal or systemic) within 30 days of enrollment 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). Vaginal or anal intercourse within 36 hours prior to enrollment Heterosexual intercourse since last menses that places the participant at risk of pregnancy (without condom use or sterilization of at least one partner) History of hysterectomy History of malignancy within the pelvis (includes uterus, cervix, vagina, and vulva) Contraindication, allergy or intolerance to use of the contraceptive desired by the participant 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Combined Oral Contraceptive pills<br>Levonorgestrel/ethinyl estradiol 0.15mg/30mcg daily oral tabs x21 then 7 inert tabs | Drug: levonorgestrel exposure<br> <br> * Other names: LNG/EE oral contraceptive pills (Levora);|
| depot medroxyprogesterone acetate<br>150mg DMPA intramuscular injection once every 3 months | Drug: DMPA exposure<br> <br> * Other names: DMPA (Depo-Provera 150mg IM);|
| Levonorgestrel-intrauterine device<br>52mg levonorgestrel intrauterine device | Drug: levonorgestrel exposure<br> <br> * Other names: LNG/EE oral contraceptive pills (Levora);Device: IUD insertion<br> <br> * Other names: Copper T-380A IUD (ParaGard);|
| Copper intrauterine device<br>Copper T380A intrauterine device | Device: IUD insertion<br> <br> * Other names: Copper T-380A IUD (ParaGard);|
| Etonogestrel contraceptive implant<br>68mg etonogestrel subdermal implant | Drug: etonogestrel exposure<br> <br> * Other names: ENG-implant (Nexplanon or Implanon);Device: subdermal contraceptive implant insertion<br> <br> * Other names: ENG-implant (Nexplanon or Implanon);|
| Control<br>Low risk of pregnancy due to sterilization, heterosexual abstinence, or consistent condom use | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification and characterization of immune cell populations and HIV-tropic receptor expression | To quantify and characterize immune cell populations and HIV-tropic receptor expression in the upper and lower genital tract and blood at baseline and after 3 and 6 months of typical contraceptive use | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing changes in the vaginal microflora within the first 6 months of contraceptive use | To describe the microflora of the upper and lower genital tracts of healthy asymptomatic women before and after 3 and 6 months of typical contraceptive use and to assess changes in the vaginal ecology within the first 6 months of contraceptive use. | baseline, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune cells, contraception, intrauterine device, IUD, copper, microflora, DMPA, etonogestrel, subdermal implant