Long-Acting Progestin Contraception and the Vaginal Microbiome

NCT02740998 | Completed DMC

• 1 other identifier: H-34707
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

Despite many years of research, controversy persists as to whether hormonal contraception promotes HIV acquisition. A number of observational studies on depot medroxyprogesterone acetate (DMPA) injection showed an increase in HIV risk and no evidence of increased risk with oral contraceptive pills. There are no human studies currently published on the impact of the levonorgestrel intrauterine device (LNG IUD) on HIV transmission risk and minimal data on the effects of the etonogestrel subdermal implant (ESI) on risk of HIV acquisition. Establishing whether any of these highly effective contraceptives increases the risk of HIV infection would have far-reaching public health implications, particularly in areas of high HIV prevalence such as sub-Saharan Africa, where injectable contraception accounts for nearly half of contraceptive use. Perturbations in the normal vaginal microbiota, or community of microorganisms inhabiting the vaginal body niche, have long been known to affect the risk of transmission of HIV. Studies have shown altered vaginal microbiota with DMPA injection and preserved vaginal microbiota with the LNG IUD, but no studies have compared these methods head-to-head or used culture-independent sequencing methodology. The investigators propose a prospective pilot study to evaluate the impact of different long-acting progestin contraceptive formulations on the vaginal microbiome. Specifically, the investigators aim to identify and compare metagenomics profiles associated with DMPA, LNG IUD, and ESI contraceptive use by community analysis of vaginal swab samples from women collected longitudinally after contraceptive method initiation. The investigators hypothesize that DMPA will increase community diversity in the vaginal microbiota, whereas the LNG IUD and ESI will not affect the balance of microorganisms in the vagina. Women who are planning to initiate DMPA, LNG IUD, and ESI contraception as well as controls not seeking contraception will be recruited for the study from Boston Medical Center (BMC), a tertiary care center with a racially and socioeconomically diverse patient population. Women will have longitudinal follow-up with self-sampling of the vagina for sexually transmitted infection testing and metagenomics analysis at method initiation, 2-3 months, and 6 months. Establishing the safest long-acting progestin contraceptive alternative will promote effective contraception use and lower rates of HIV acquisition worldwide.

Conditions

Sexually Transmitted Infection

Keywords

Microbiome; Progestin; Long-acting contraception

Outcome Measures

Primary Outcomes (1)

• Biomarker discovery

  Use of the following two approaches will provide preliminary data for future larger studies from this limited pilot study. If the hypothesis of a vaginal microbial shift with Depo Provera (DMPA) use is confirmed (our PRIMARY analysis), these tools will enable visualization of the differences. The tables of relative abundance of either taxonomic groups or metabolic pathways will be used to identify differential bacterial biomarkers present among patient and sample classes. Two bioinformatics tools particularly useful for biomarker discovery are LEfSe and MaAsLin (Multivariate Association with Linear Models, http://huttenhower.sph.harvard.edu/maaslin).

  1 year

Secondary Outcomes (1)

• Correlation of disease state and metadata factors with microbiome structure

  1 Year

Other Outcomes (1)

• Site based approach to the analysis of the impact of disease status and metadata

  1 Year

Study Arms (4)

Depo Provera

Ten women ages 18-40 who elect to start a using Depo Provera for contraception.

Mirena IUD

Ten women ages 18-40 who elect to start a using a Mirena IUD for contraception.

Nexplanon

Ten women ages 18-40 who elect to start a using Nexplanon for contraception.

Control: Tubal Sterilization

Five women ages 18-40 who elect to have a tubal sterilization.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Women between the ages of 18-40 initiating long-acting progestin contraception or who are seeking tubal sterilization will be enrolled at a routine office visit at the ambulatory practice/family planning clinic.

You may qualify if:

• Women between the ages of 18-40 who elect to start a long-acting progestin contraceptive or who opt for tubal sterilization.
• Our site will enroll 18 patients total: 5 DMPA; 5 Mirena IUD, 5 Nexplanon, 2-3 tubal ligations/Essures (controls)

You may not qualify if:

• Non-English-speaking without translator
• Current or recent (within past 3 months) use of hormonal contraception
• Currently menstruating
• Vaginal intercourse within 48 hours of visit
• Known or suspected pregnancy, or pregnancy within the past 6 weeks.
• Use of progestin method for primary indication other than contraception (e.g. pelvic pain, menorrhagia)
• Current STI or vaginitis (yeast or BV)
• Tampon usage
• Regular douching
• Chronic antibiotic use within past 4 weeks
• HIV positive
• Immunosuppressive therapy (organ transplant, chemotherapy)

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (2)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Vaginal swabs for microbiome analysis and sexually transmitted infection testing.

MeSH Terms

Conditions

Sexually Transmitted Diseases

Condition Hierarchy (Ancestors)

Communicable Diseases; Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wendy Kuohung, MD

  Boston 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 of Ob/Gyn

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 18, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: July 17, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)