Clinical trial NCT03660046: Contraceptive Hormones, Immunity, and Microbiome Evaluation
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hormonal Contraception
Keywords: Human immunodeficiency virus
Sexually Transmitted Diseases
Contraceptives
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-09-06
Enrollment: 155
Sex: FEMALE
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be selected from several sites in the greater Atlanta community to include: family planning clinics, OB/GYN practice/reproductive heath clinics, community based recruitment through postings at community centers, community health fairs, coffee shops and local universities, as well as web-based recruitment through the national ResearchMatch.

Brief 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.

Detailed 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).

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: Week 1 and Week 3 (pre contraception), and 13 and 15 weeks after initiating contraception
measure: Change in Nugent's score among the three intervention groups pre and post contraception
timeFrame: Week 1 and Week 3 (pre contraception), and 13 and 15 weeks after initiating contraception
measure: Percent of expression of 16S rRNA gene sequencing among the three intervention groups pre and post contraception
timeFrame: Week 1 and Week 3 (pre contraception), and 13 and 15 weeks after initiating contraception
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic, Bldg A., 2nd Floor, 1365 Clifton Road, NE
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Women's Center
state: Georgia
Study officials:
affiliation: Emory University
name: Alicia Smith, PhD
role: PRINCIPAL_INVESTIGATOR
References: