Bacterial VaginosisPhase 1NCT02527941
Effect of Bacterial Vaginosis on HIV Susceptibility and Female Genital Immunology
A Phase 1 study testing Metronidazole in people with Bacterial Vaginosis and HIV Infections, run by University of Toronto at 1 site in Kenya.
Trial summary
A non-randomized, interventional, longitudinal clinical study to quantify the impact of bacterial vaginosis treatment on HIV susceptibility and genital immunology in Kenyan women. Read more about this study
- Who is it for?
- Ages 18 to 49 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Bacterial Vaginosis, HIV Infections
- What is being tested?
- Metronidazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteKenya
- Study dates
- Aug 2015to Nov 2015
- Phase
- Phase 1
- 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 49 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants are over 18 years of age, not pregnant and willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
- Willing to comply with the requirements of the protocol
- HIV and classical STI (see below) negative
- test positive for BV, defined as Nugent score from 7-10
- willing to take oral metronidazole twice a day for 7 days
- willing to abstain from alcohol during and for 48 hours after metronidazole treatment
Who cannot join
- HIV infected
- Deemed by physician to be unlikely to complete study protocol.
- Pregnant.
- Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
- Tested positive for classical STIs or having genital ulcers
- Prior hysterectomy
- Contraindication, allergy or intolerance to use of metronidazole
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology
A non-randomized, interventional, longitudinal clinical study to quantify the impact of bacterial vaginosis treatment on HIV susceptibility and genital immunology in Kenyan women.
Read the detailed description
Bacterial Vaginosis (BV), defined as an alteration in the normal vaginal bacteria ("microbiome"), is characterized by a reduction of hydrogen peroxide-producing gram-positive lactobacilli and overgrowth of gram-negative and anaerobic bacteria. BV is more prevalent in SSA and usually recurs soon after treatment. BV is associated with vaginal inflammation, an increased HIV acquisition risk among uninfected women, and increased HIV transmission to the male sexual partner of a co-infected woman. Therefore, BV may be responsible for up to 17% of HIV transmission events in SSA.
There are several hypotheses for the mechanisms by which BV may increase the risk of HIV acquisition. These include the disruption of mucosal barrier, alteration of protective innate immunity, and increased number and/or susceptibility of HIV target cells in the genital mucosa. Longitudinal studies that address the mechanisms by which the vaginal microbiota alters host mucosal immunology and HIV risk will help us better understand the impact of BV and it's treatment on mucosal immunology and HIV susceptibility. The goal of this non-randomized, interventional, longitudinal clinical study is to use a novel ex vivo HIV infectivity assay developed in the Kaul lab to quantify the effect of BV and its treatment on HIV susceptibility and genital immunology in HIV-uninfected women from Nairobi, Kenya. Fifty HIV, STI-uninfected women with bacterial vaginosis on Nugent scoring will be provided with one week of metronidazole 400mg po three times daily (as per Kenyan National Guidelines). Cytobrush and vaginal SoftCup sampling will be performed at baseline and 4 weeks after treatment initiation, at the same stage of the menstrual cycle. The primary endpoint will be pseudovirus entry into cervix-derived CD4+ T cells. Secondary endpoints will include a pre-defined cervico-vaginal inflammation score; genital CD4+ T cell immune characteristics; the genital microbiome; the genital proteome.
- Conditions
- Bacterial Vaginosis, HIV Infections
- Being tested
- Metronidazole
- Keywords
- Genital immunology, HIV susceptibility, Microbiome, Bacterial vaginosis, Virus entry assay
- Medical subject headings
- Vaginosis, Bacterial, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetronidazoleDrug
Also called flagyl
Participants will be provided with oral metronidazole 400mg po tid for one week, and followed up one month after treatment initiation.
| Study group | Role | What they receive |
|---|---|---|
| metronidazole | Experimental | 50 women who test negative for HIV and classical sexually transmitted infections but test positive for Bacterial Vaginosis will be treated with metronidazole at a dosage of 400mg/dose, 3 doses per day, for 7 days (as per Kenyan National Guidelines). Receives: Drug: Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent HIV pseudovirus entry into cervical CD4+ T cells.
The percentage of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
Measured: up to 8 months
Total number of cervical CD4+ T cells infected ex vivo with HIV.
The total number of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
Measured: up to 8 months
Secondary outcomes (4)
A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines.
Level of 14 genital cytokines/chemokines (GM-CSF, IL-1a, IL-8, MCP-1, MIG, MIP-3a, RANTES, IL-10, IL-17, IL-1b, IL-6, IP-10, MIP-1b, TNF-a) will be combined into a genital inflammation score [Arnold K et al, Muc Immunol, 2015].
Measured: up to 8 months
The cervico-vaginal microbiome.
The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after metronidazole therapy.
Measured: up to 8 months
Genital proteome analysis.
The genital proteome will be assessed by mass spectroscopy before and after metronidazole therapy.
Measured: up to 8 months
CD4+ expression of pre-defined HIV susceptibility markers
Surface expression of CCR5, CD69, a4b7 and a4b1 by endocervical CD4 T cells before and after metronidazole therapy.
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bacterial VaginosisStudies of the same condition, open and under way.
- More trials run by University of TorontoThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rupert Kaul, University of Toronto
- Investigators
- Rupert Kaul, MD/PhD, Principal investigator, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527941
- Sponsor's protocol ID
- UTorontoBV
- Status last verified
- Feb 2016
- First submitted
- 14 Aug 2015
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology
- ClinicalTrials.gov ID
- NCT02527941
- Acronym / sponsor ID
- UTorontoBV
- Conditions
- Bacterial Vaginosis, HIV Infections
- Keywords
- Genital immunology, HIV susceptibility, Microbiome, Bacterial vaginosis, Virus entry assay
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 19 Aug 2015 (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.
A non-randomized, interventional, longitudinal clinical study to quantify the impact of bacterial vaginosis treatment on HIV susceptibility and genital immunology in Kenyan women.
Detailed description
Bacterial Vaginosis (BV), defined as an alteration in the normal vaginal bacteria ("microbiome"), is characterized by a reduction of hydrogen peroxide-producing gram-positive lactobacilli and overgrowth of gram-negative and anaerobic bacteria. BV is more prevalent in SSA and usually recurs soon after treatment. BV is associated with vaginal inflammation, an increased HIV acquisition risk among uninfected women, and increased HIV transmission to the male sexual partner of a co-infected woman. Therefore, BV may be responsible for up to 17% of HIV transmission events in SSA.
There are several hypotheses for the mechanisms by which BV may increase the risk of HIV acquisition. These include the disruption of mucosal barrier, alteration of protective innate immunity, and increased number and/or susceptibility of HIV target cells in the genital mucosa. Longitudinal studies that address the mechanisms by which the vaginal microbiota alters host mucosal immunology and HIV risk will help us better understand the impact of BV and it's treatment on mucosal immunology and HIV susceptibility. The goal of this non-randomized, interventional, longitudinal clinical study is to use a novel ex vivo HIV infectivity assay developed in the Kaul lab to quantify the effect of BV and its treatment on HIV susceptibility and genital immunology in HIV-uninfected women from Nairobi, Kenya. Fifty HIV, STI-uninfected women with bacterial vaginosis on Nugent scoring will be provided with one week of metronidazole 400mg po three times daily (as per Kenyan National Guidelines). Cytobrush and vaginal SoftCup sampling will be performed at baseline and 4 weeks after treatment initiation, at the same stage of the menstrual cycle. The primary endpoint will be pseudovirus entry into cervix-derived CD4+ T cells. Secondary endpoints will include a pre-defined cervico-vaginal inflammation score; genital CD4+ T cell immune characteristics; the genital microbiome; the genital proteome.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| metronidazole | Experimental | Drug: Metronidazole50 women who test negative for HIV and classical sexually transmitted infections but test positive for Bacterial Vaginosis will be treated with metronidazole at a dosage of 400mg/dose, 3 doses per day, for 7 days (as per Kenyan National Guidelines). |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participants are over 18 years of age, not pregnant and willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
- Willing to comply with the requirements of the protocol
- HIV and classical STI (see below) negative
- test positive for BV, defined as Nugent score from 7-10
- willing to take oral metronidazole twice a day for 7 days
Key exclusion criteria (7 listed)
- HIV infected
- Deemed by physician to be unlikely to complete study protocol.
- Pregnant.
- Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
- Tested positive for classical STIs or having genital ulcers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetronidazoleAlso: flagylParticipants will be provided with oral metronidazole 400mg po tid for one week, and followed up one month after treatment initiation. | Drug | metronidazole |
Primary outcome
Percent HIV pseudovirus entry into cervical CD4+ T cells.
Time frame: up to 8 months
The percentage of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
Total number of cervical CD4+ T cells infected ex vivo with HIV.
Time frame: up to 8 months
The total number of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
4 secondary outcomes
A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines.
Time frame: up to 8 months
The cervico-vaginal microbiome.
Time frame: up to 8 months
Genital proteome analysis.
Time frame: up to 8 months
CD4+ expression of pre-defined HIV susceptibility markers
Time frame: up to 8 months
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 10 Feb 2016.
Related trials for Bacterial Vaginosis
Enrolling by invitationObservational study
Prevention of Vaginal Cuff Infection After Hysterectomy by Addition of Vaginal Clindamycin
Surgical Site Infection, Vaginal Cuff Cellulitis
Not yet recruitingPhase 2
WST03 Capsule Combined With Metronidazole for Bacterial Vaginosis
Bacterial Vaginosis (BV)
RecruitingPhase 1
A Randomized, Multicenter, Open-label, Active-controlled Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Multiple Intravaginal Doses of GenSci142 in Patients With Bacterial Vaginosis (BV)
Randomized, Open-label
Not yet recruitingPhase 1
A Study to Test New Investigational Drugs (LCFA-01and LC103) for Bacterial Vaginosis (BV) Treatment
Bacterial Vaginosis
Recruiting
Multi-Gyn ActiGel Plus for Treatment of Bacterial Vaginosis
Bacterial Vaginoses
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.
Rupert Kaul, MD/PhD principal investigator
University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metronidazole in people with Bacterial Vaginosis and HIV Infections, run by University of Toronto at 1 site in Kenya.
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 6 inclusion and 7 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 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Percent HIV pseudovirus entry into cervical CD4+ T cells. (time frame: up to 8 months). The study lists 2 primary outcomes in all. 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 10 Feb 2016; AzTrials last refreshed its copy on 8 Nov 2026.