Contraceptive Hormones, Immunity, and Microbiome Evaluation

NCT03660046 | Completed DMC FDA Drug

• 2 other identifiers: IRB00104017R01HD095741-01A1
• Study Type: observational
• Target: 155
• Locations: 1 country
• Sites: 3

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.

Conditions

Hormonal Contraception

Keywords

Human immunodeficiency virus; Sexually Transmitted Diseases; Contraceptives

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Study Arms (3)

Depot medroxyprogesterone acetate (DMPA)

This arm includes subjects that choose Depot medroxyprogesterone acetate (DMPA) as contraception.

Drug: Depot medroxyprogesterone acetate (DMPA)

Etonogestrel implant (Eng-Implant)

This arm includes subjects that choose Etonogestrel implant (Eng-Implant) as contraception.

Drug: Etonogestrel implant (Eng-Implant)

Levonorgestrel IUD (Lng-IUD)

This arm includes subjects that choose Levonorgestrel Intrauterine device (Lng-IUD) as contraception.

Drug: Levonorgestrel IUD (Lng-IUD)

Interventions

Depot medroxyprogesterone acetate (DMPA) DRUG

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

Also known as: Medroxyprogesterone acetate (MPA), Depo-Provera

Depot medroxyprogesterone acetate (DMPA)

Etonogestrel implant (Eng-Implant) DRUG

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.

Also known as: Nexplanon

Etonogestrel implant (Eng-Implant)

Levonorgestrel IUD (Lng-IUD) DRUG

The Levonorgestrel Intrauterine Device (Lng-IUD) (Mirena or copper) will be placed at study week 3 by Dr. Haddad or a trained clinician.

Also known as: Mirena, Copper

Levonorgestrel IUD (Lng-IUD)

Eligibility Criteria

• Age: Up to 45 Years
• Gender Eligibility Details: Female sex, defined by sex at birth
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

The Emory Clinic, Bldg A., 2nd Floor, 1365 Clifton Road, NE

Atlanta, Georgia, 30322, United States

Location

Atlanta Women's Center

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Sexually Transmitted Diseases

Interventions

Medroxyprogesterone Acetate; etonogestrel; Levonorgestrel; Copper

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Alicia Smith, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 6, 2018
• Study Start: December 7, 2018
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)