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

Not Applicable

Completed

• Conditions: Genital Tract Microflora; Genital Tract Mucosal Immunity
• Interventions: Drug: IUD placement; Drug: Levonorgestrel IUD; Drug: Copper T380A IUD

• Registration Number: NCT01240811
• Lead Sponsor: Sharon Achilles

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-11
• Study First Submitted QC: 2010-11-12
• Study First Posted: 2010-11-15
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Results First Submitted: 2013-01-15
• Results First Submitted QC: 2013-06-17
• Results First Posted: 2013-07-22
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-29
• Last Update Posted: 2017-12-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 42

Inclusion Criteria

1. Non-pregnant, healthy females who are seeking an IUD for contraception
2. Age 18-40 years, inclusive at the time of enrollment
3. 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
4. Willing and able to sign the informed consent and to comply with the study protocol

Inclusion criteria for healthy control subjects:

1. Non-pregnant, healthy females
2. Age 18-40 years, inclusive at the time of enrollment
3. 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
4. Willing and able to sign the informed consent and to comply with the study protocol
5. Prior surgical sterilization or heterosexually abstinent

Exclusion Criteria

1. Use of any hormonal or intrauterine contraceptive method within the past two months

2. Use of DMPA within the past 10 months

3. 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

4. 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)

5. Active HSV/ulcerative disease in the genital tract or perineum

6. History of immunosuppression (diabetes, HIV, chronic steroid use)

7. Use of vaginal product (N9, microbicide, douche, antifungal, steroid, or hormone) within the past 30 days

8. Use of any systemic or vaginal steroid or antibiotic within the past 30 days

9. Vaginal or anal intercourse within 1 week of sample collection

10. Heterosexual vaginal intercourse since last menses without condom use

11. History of hysterectomy

12. History of malignancy in the uterus or cervix

13. Uterine anomaly (bicornuate uterus, uterine septum, or uterine didelphys)

14. Allergy to copper and/or intolerance to levonorgestrel

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Levonorgestrel IUS	IUD placement	Healthy volunteers seeking contraception with IUD. Randomized to LNG IUS.
Levonorgestrel IUS	Levonorgestrel IUD	Healthy volunteers seeking contraception with IUD. Randomized to LNG IUS.
Copper T380A IUD	Copper T380A IUD	Healthy volunteers seeking contraception with IUD. Randomized to Copper T380A IUD.
Copper T380A IUD	IUD placement	Healthy volunteers seeking contraception with IUD. Randomized to Copper T380A IUD.

Primary Outcome Measures

Name	Time	Method
%CD4 Expressing CCR5 HIV Co-receptor in the Cervix and Endometrium	2 months	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

Secondary Outcome Measures

Name	Time	Method
Change in Quantities of Vaginal H2O2-producing Lactobacillus Species and Gardnerella Vaginalis	2 Months	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.
Change in Vaginal Flora	2 Months	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.

Trial Locations

Locations (1)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States