Contraceptive Hormones, Immunity, and Microbiome Evaluation

Hormonal Contraception Clinical Trial

— CHIME  

Official title:

A Prospective Cohort Study Evaluating the Impact of Three Progestin-based Hormonal Contraceptive (HC) Methods on Immunologic Changes in the Female Genital Tract (FGT) and Systemically

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03660046
• Other study ID #: IRB00104017
• Secondary ID: R01HD095741-01A1
• Status: Recruiting
• Start date: December 7, 2018
• Est. completion date: September 2024

Study information

• Verified date: September 2023
• Source: Emory University
• Contact: Alicia Smith, PhD
• Phone: 404-712-5006
• Email: alicia.smith[@]emory.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study is a prospective cohort study to explore the mechanisms underlying the HIV risk associated with pharmacologic doses of exogenous sex hormones via hormonal contraceptives specially progestin-containing hormonal contraception (HC). The study seeks to test that HC induce immunologic changes capable of altering HIV susceptibilities, that these effects will vary by contraceptive type, and that they will be modified by the vaginal microenvironment.

Description:

This study is a translational research project to explore the mechanisms underlying the HIV risk associated with pharmacologic doses of exogenous sex hormones (via hormonal contraceptives). Emerging data suggests that certain hormonal contraceptives may induce mucosal and systemic immune changes that could increase the risk of infection with HIV. While several studies have aimed to characterize immunologic changes in women using hormonal contraceptives, the nature and the magnitude of these immune changes have not been adequately defined due to limitations in study design rigor, and small and statistically underpowered sample sizes.

The study will prospectively recruit cohorts of HIV-uninfected women initiating hormonal contraception to characterize systemic and lower genital tract innate and adaptive immunologic changes that occur over a course of up to 4 months. This study will test the overarching hypothesis that hormonal contraceptives induce systemic and mucosal immune changes capable of altering susceptibilities and/or responses to diseases including HIV infection, and that these effects vary markedly in nature and magnitude by contraceptive type and will be modified by the vaginal microenvironment. The main aim is to determine the immunologic alterations in female genital and systemic immune profile associated with depot medroxyprogesterone acetate (DMPA), Etonogestrel implant (Eng-Implant) and Levonorgestrel IUD (Lng-IUD).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A to 45 Years

Eligibility

Inclusion Criteria:

• Female sex, defined by sex at birth.

• Age = 45 years. If < 18 years of age, participant must be capable of providing assent, understanding and complying with all study procedures, and have written informed consent from a parent or legal guardian.

• Normal menses (occurring within 22-35 day intervals) for > 2 cycles. Women who are postpartum or post-abortion who have resumed menses are eligible.

• Intact uterus and cervix.

• Interested in initiating HC and willing to accept DMPA, Eng-Implant or Lng-IUD.

• Willing to delay initiation of HC for up to 1 month.

• Able and willing to provide informed consent, and undergo study procedures.

• Negative HIV test by Ora-Quick© method at Screening Visit.

• Agree to abstain from vaginal intercourse or using intra-vaginal products for 1 day prior to each study visit.

Exclusion Criteria:

• Pregnant or planning to become pregnant within the next year.

• Breastfeeding, if not having active menstrual cycles. Breastfeeding is not exclusionary if the participant is actively cycling.

• History of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery within the past year.

• Current use of systemic HC or IUD, based on self-report and/or hormonal testing.

• Taking concurrent medications that interact with selected HC.

• Contraindications to selected contraceptive per the Center for Disease Control medical eligibility criteria or judgment of clinician.

• Allergy to lidocaine for cervical biopsies (if consenting to optional biopsies).

Related Conditions & MeSH terms

• Hormonal Contraception

Intervention

Drug:
• Depot medroxyprogesterone acetate (DMPA)
Depot medroxyprogesterone acetate (DMPA) will be dispensed from the Grady Pharmacy Service and will be administered every 12 weeks at the standard dose of 150 mg Intramuscular injection, beginning from week 3 of study enrollment and repeated every 13 weeks
• Etonogestrel implant (Eng-Implant)
A standard Nexplanon rod Implant that is a subdermal implant in the arm. This will be placed at study week 3 by Dr. Haddad or a trained clinician. It contains Etonogestrel 68mg.
• Levonorgestrel IUD (Lng-IUD)
The Levonorgestrel Intrauterine Device (Lng-IUD) (Mirena or copper) will be placed at study week 3 by Dr. Haddad or a trained clinician.

Locations

Country	Name	City	State
United States	Atlanta Women's Center	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	The Emory Clinic, Bldg A., 2nd Floor, 1365 Clifton Road, NE	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mean total leukocytes and CD4+ T-cells expressing CCR5 in the lower female genital tract (FGT) among the three intervention groups pre and post contraception	Using Fortessa flow cytometer and Luminex, effector memory Cluster Differentiation 4 (CD4) + Thymocytes (T) cells will be analyzed for surface expression of HIV coreceptors cell surface receptor C-C chemokine receptor type 5 (CCR5) and reported as percent of total leukocytes and CD4+ T-cells. The cytometry will use the cervicovaginal fluid (CVF) collected by cervicovaginal lavage (CVL).This test will characterize the alterations in female genital and systemic immune profiles associated with three long-acting progestin-only Hormonal Contraception.	Week 1 and Week 3 (pre contraception), and 13 and 15 weeks after initiating contraception
Primary	Change in Nugent's score among the three intervention groups pre and post contraception	The Nugent Score is a Gram stain scoring system for vaginal swabs to diagnose bacterial vaginosis. The Nugent score is calculated by 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). A score of 7 to 10 is consistent with bacterial vaginosis without culture.	Week 1 and Week 3 (pre contraception), and 13 and 15 weeks after initiating contraception
Primary	Percent of expression of 16S rRNA gene sequencing among the three intervention groups pre and post contraception	16 Svedberg ribosomal RNA (16S rRNA) is the component of the 30 Svedberg ribosomal RNA (30S rRNA) small subunit of a prokaryotic ribosome that binds to the Shine-Dalgarno sequence. The genes coding for it are referred to as 16S rRNA gene and are used in reconstructing phylogenies. 16S rRNA gene sequence analysis can better identify poorly described, rarely isolated, or phenotypically aberrant strains, can be routinely used for identification of mycobacteria, and can lead to the recognition of novel pathogens and uncultured bacteria.The term 16S refers to how it settles to when centrifuged (it's called a sedimentation rate, and it's measured in Svedberg (S) units).	Week 1 and Week 3 (pre contraception), and 13 and 15 weeks after initiating contraception