Study of Immune Cell Changes in the Genital Tract 2 Months After Initiation of an IUD for Contraception

Study Overview
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Brief Summary
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This pilot study is being performed to investigate the influence that starting contraception with an IUD has on the local immune cell populations and features, with a particular focus on the cells and cell-surface features that are important in HIV transmission (CD4 cells and CCR5 cell receptors). Based on results from large epidemiologic studies there seems to be a consistent finding of slightly increased HIV acquisition in women who use hormonal contraception. It is not clear if this is due to a biological phenomenon or if it relates to a difference in sexual behaviors/risks of women on hormonal contraceptives. The study hypothesis is that CD4 cells and CCR5 HIV-tropic receptor density increases within the upper and lower genital tract of women 2 months after placement of progestin-containing intrauterine devices for contraception as compared with women not using hormonal contraception.

Official Title
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Impact of Intrauterine Contraception on the Immune Environment of the Female Genital Tract

Conditions
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Genital Tract Mucosal Immunity, Genital Tract Microflora

Intervention / Treatment
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* Drug: IUD placement
* Drug: Levonorgestrel IUD
* Drug: Copper T380A IUD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-pregnant, healthy females who are seeking an IUD for contraception Age 18-40 years, inclusive at the time of enrollment History of regular menstrual 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 Willing and able to sign the informed consent and to comply with the study protocol Inclusion criteria for healthy control subjects: Non-pregnant, healthy females Age 18-40 years, inclusive at the time of enrollment History of regular menstrual 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 Willing and able to sign the informed consent and to comply with the study protocol Prior surgical sterilization or heterosexually abstinent Exclusion Criteria: Use of any hormonal or intrauterine contraceptive method within the past two months Use of DMPA within the past 10 months Any of the following within the past two months: Pregnancy or breastfeeding Surgery/biopsy of the vulva, vagina, or cervix History of STI New sexual partner Evidence of vaginal/pelvic infection on screening Abnormal wet mount (see description above) Pelvic exam findings clinically consistent with infection Positive screen for Gc, Ct, or HIV (will be excluded post randomization) Active HSV/ulcerative disease in the genital tract or perineum History of immunosuppression (diabetes, HIV, chronic steroid use) Use of vaginal product (N9, microbicide, douche, antifungal, steroid, or hormone) within the past 30 days Use of any systemic or vaginal steroid or antibiotic within the past 30 days Vaginal or anal intercourse within 1 week of sample collection Heterosexual vaginal intercourse since last menses without condom use History of hysterectomy History of malignancy in the uterus or cervix Uterine anomaly (bicornuate uterus, uterine septum, or uterine didelphys) Allergy to copper and/or intolerance to levonorgestrel

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control-No IUD<br>Healthy volunteers not at risk of pregnancy and not using any hormonal contraception. | |
| Experimental: Levonorgestrel IUS<br>Healthy volunteers seeking contraception with IUD. Randomized to LNG IUS. | Drug: IUD placement<br>* Volunteer subjects who are not at risk of pregnancy because they are either surgically sterilized or heterosexually abstinent will be enrolled into the control group (no intervention). All other volunteers will be seeking an IUD for contraception and will be randomized to LNG-IUD (Mirena) or Copper IUD (ParaGard).<br>Drug: Levonorgestrel IUD<br> <br> * Other names: Mirena IUD;|
| Experimental: Copper T380A IUD<br>Healthy volunteers seeking contraception with IUD. Randomized to Copper T380A IUD. | Drug: IUD placement<br>* Volunteer subjects who are not at risk of pregnancy because they are either surgically sterilized or heterosexually abstinent will be enrolled into the control group (no intervention). All other volunteers will be seeking an IUD for contraception and will be randomized to LNG-IUD (Mirena) or Copper IUD (ParaGard).<br>Drug: Copper T380A IUD<br> <br> * Other names: ParaGard IUD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| %CD4 Expressing CCR5 HIV Co-receptor in the Cervix and Endometrium | Change in CCR5 expression on T-lymphocytes 2 months after insertion of IUD (either hormonal LNG-IUD or non-hormonal Cu-IUD) in cervix and endometrium as measured by flow cytomety | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vaginal Flora | Changes in vaginal flora as assessed by Nugent score The Nugent score is calculated by microscopically assessing for the presence of large Gram-positive rods (Lactobacillus morphotypes; decrease in Lactobacillus scored as 0 to 4), small Gram-variable rods (Gardnerella vaginalis morphotypes; scored as 0 to 4), and curved Gram-variable rods (Mobiluncus spp. morphotypes; scored as 0 to 2) and can range from 0 to 10. A score of 7 to 10 is consistent with bacterial vaginosis, 4-6 is consistent with intermediate vaginal flora, and 0-3 is normal vaginal flora. | 2 Months | 
| Change in Quantities of Vaginal H2O2-producing Lactobacillus Species and Gardnerella Vaginalis | Changes in vaginal flora as assessed by qPCR quantitation of H2O2 producing Lactobacilli species and Gardnerella vaginalis. Quantitative PCR (qPCR) results are reported as log concentration of gene copies/swab specimen. | 2 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intrauterine device, IUD, levonorgestrel, copper, CD4, CCR5, microflora