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

• ClinicalTrials.gov Identifier: NCT01240811
• Recruitment Status: Completed
• First Posted: November 15, 2010
• Results First Posted: July 22, 2013
• Last Update Posted: December 26, 2017
• Sponsor: Sharon Achilles
• Information provided by (Responsible Party): Sharon Achilles, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Genital Tract Mucosal Immunity; Genital Tract Microflora	Drug: IUD placement; Drug: Levonorgestrel IUD; Drug: Copper T380A IUD	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Impact of Intrauterine Contraception on the Immune Environment of the Female Genital Tract
• Study Start Date: November 2010
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Control-No IUD; Healthy volunteers not at risk of pregnancy and not using any hormonal contraception.
Experimental: Levonorgestrel IUS; Healthy volunteers seeking contraception with IUD. Randomized to LNG IUS.	Drug: IUD placement; 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).; Drug: Levonorgestrel IUD; Other Name: Mirena IUD
Experimental: Copper T380A IUD; Healthy volunteers seeking contraception with IUD. Randomized to Copper T380A IUD.	Drug: IUD placement; 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).; Drug: Copper T380A IUD; Other Name: ParaGard IUD

Outcome Measures

Primary Outcome Measures :

1. %CD4 Expressing CCR5 HIV Co-receptor in the Cervix and Endometrium [ Time Frame: 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 :

1. Change in Vaginal Flora [ Time Frame: 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.
2. Change in Quantities of Vaginal H2O2-producing Lactobacillus Species and Gardnerella Vaginalis [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Sharon Achilles

Investigators

• Principal Investigator: Sharon Achilles, MD, PhD; University of Pittsburgh

More Information

• Responsible Party: Sharon Achilles, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01240811
• Other Study ID Numbers: PRO09100199
• First Posted: November 15, 2010
• Results First Posted: July 22, 2013
• Last Update Posted: December 26, 2017
• Last Verified: November 2017

Keywords provided by Sharon Achilles, University of Pittsburgh:

intrauterine device; IUD; levonorgestrel; copper; CD4; CCR5; microflora

Additional relevant MeSH terms:

Copper; Levonorgestrel; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Trace Elements; Micronutrients