Sexually Transmitted InfectionvMICRObNCT02740998
Long-Acting Progestin Contraception and the Vaginal Microbiome
An observational study of Sexually Transmitted Infection, run by Boston Medical Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Sexually Transmitted Infection
- How many people
- 28 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2016to 1 Jun 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 12Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston Medical Center
Boston, Massachusetts, 02118
Women and Infants Hospital
Providence, Rhode Island, 02905
About this study
Official title: Impact of Long-Acting Progestin Contraception on the Vaginal Microbiome
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.
Read the detailed description
Women between the ages of 18-45 initiating long-acting progestin contraception will be enrolled at a routine office visit at the family planning clinics of each institution. Enrollment will begin in April 2016 and will stop after 6 months to allow for longitudinal follow-up and analyses. For this pilot study, a total of 30 long-acting progestin contraceptive initiators with 10 subjects in each method group (DMPA, LNG IUD, ESI) and 5 age-matched, controls seeking tubal sterilization will be selected for longitudinal STI screening and vaginal sampling for microbiome analysis.
After consent is obtained, trained staff will interview subjects using a brief sociodemographic/habits questionnaire that includes questions on age, race, body mass index, smoking status, history of sexually transmitted infections and yeast vaginitis, weekly frequency of coitus, and number of lifetime sexual partners. Subjects will be instructed to self-sample the vagina at three timepoints: 1) at method initiation, 2) 2-3 months later, and 3) 6 months later. Self-collected vaginal swab specimens will be assayed for Trichomonas vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae using DNA amplification in the clinical lab. Microbiome samples collected at each timepoint will be analyzed and compared to the initiation sample to detect longitudinal differences.
- Conditions
- Sexually Transmitted Infection
- Keywords
- Microbiome, Progestin, Long-acting contraception
- Medical subject headings
- Sexually Transmitted Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 year
Secondary outcomes (1)
Correlation of disease state and metadata factors with microbiome structure
Effects of different sources of variation (e.g. smoking status, presence of STI) on community structure will be assessed in MANOVA models, and for OTUs of interest, ANOVA. Analyses will use either frequencies of OTUs or PCA values from major axes. Effects of various sources of variation on community diversity will be analyzed by ANOVA on diversity indices, obtained from QIIME.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2016 (estimated)
- Study startMar 2016
- Primary completion1 Jun 2018
- Study completion1 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sexually Transmitted InfectionStudies of the same condition, open and under way.
- More trials run by Boston Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wendy Kuohung, Boston Medical Center
- Investigators
- Wendy Kuohung, MD, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02740998
- Sponsor's protocol ID
- H-34707
- Acronym
- vMICROb
- Status last verified
- Jul 2018
- First submitted
- 29 Mar 2016
- Last updated
- 17 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Long-Acting Progestin Contraception on the Vaginal Microbiome
- ClinicalTrials.gov ID
- NCT02740998
- Acronym / sponsor ID
- vMICROb / H-34707
- Conditions
- Sexually Transmitted Infection
- Keywords
- Microbiome, Progestin, Long-acting contraception
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Boston Medical CenterUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- 1 Jun 2018 (actual)
- Study completion
- 1 Jun 2018 (actual)
- First posted
- 18 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Women between the ages of 18-45 initiating long-acting progestin contraception will be enrolled at a routine office visit at the family planning clinics of each institution. Enrollment will begin in April 2016 and will stop after 6 months to allow for longitudinal follow-up and analyses. For this pilot study, a total of 30 long-acting progestin contraceptive initiators with 10 subjects in each method group (DMPA, LNG IUD, ESI) and 5 age-matched, controls seeking tubal sterilization will be selected for longitudinal STI screening and vaginal sampling for microbiome analysis.
After consent is obtained, trained staff will interview subjects using a brief sociodemographic/habits questionnaire that includes questions on age, race, body mass index, smoking status, history of sexually transmitted infections and yeast vaginitis, weekly frequency of coitus, and number of lifetime sexual partners. Subjects will be instructed to self-sample the vagina at three timepoints: 1) at method initiation, 2) 2-3 months later, and 3) 6 months later. Self-collected vaginal swab specimens will be assayed for Trichomonas vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae using DNA amplification in the clinical lab. Microbiome samples collected at each timepoint will be analyzed and compared to the initiation sample to detect longitudinal differences.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Biomarker discovery
Time frame: 1 year
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 secondary outcome
Correlation of disease state and metadata factors with microbiome structure
Time frame: 1 Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wendy Kuohung, MD principal investigator
Boston University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sexually Transmitted Infection, run by Boston Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker discovery (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2018.