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Trial record 45 of 54 for:    "Vaginitis" | "Metronidazole"

Effect of Bacterial Vaginosis on HIV Susceptibility and Female Genital Immunology

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ClinicalTrials.gov Identifier: NCT02527941
Recruitment Status : Completed
First Posted : August 19, 2015
Last Update Posted : February 10, 2016
Sponsor:
Information provided by (Responsible Party):
Rupert Kaul, University of Toronto

Brief 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.

Condition or disease Intervention/treatment Phase
Bacterial Vaginosis HIV Infections Drug: Metronidazole Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology
Study Start Date : August 2015
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: metronidazole
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).
Drug: Metronidazole
Participants will be provided with oral metronidazole 400mg po tid for one week, and followed up one month after treatment initiation.
Other Name: flagyl




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines. [ Time Frame: up to 8 months ]
    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].

  2. The cervico-vaginal microbiome. [ Time Frame: up to 8 months ]
    The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after metronidazole therapy.

  3. Genital proteome analysis. [ Time Frame: up to 8 months ]
    The genital proteome will be assessed by mass spectroscopy before and after metronidazole therapy.

  4. CD4+ expression of pre-defined HIV susceptibility markers [ Time Frame: up to 8 months ]
    Surface expression of CCR5, CD69, a4b7 and a4b1 by endocervical CD4 T cells before and after metronidazole therapy.



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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 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.
  2. Willing to comply with the requirements of the protocol
  3. HIV and classical STI (see below) negative
  4. test positive for BV, defined as Nugent score from 7-10
  5. willing to take oral metronidazole twice a day for 7 days
  6. willing to abstain from alcohol during and for 48 hours after metronidazole treatment

Exclusion Criteria:

  1. HIV infected
  2. Deemed by physician to be unlikely to complete study protocol.
  3. Pregnant.
  4. Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
  5. Tested positive for classical STIs or having genital ulcers
  6. Prior hysterectomy
  7. Contraindication, allergy or intolerance to use of metronidazole

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527941


Locations
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Kenya
Kenya AIDS Vaccine Initiative Clinic
Nairobi, Kenya
Sponsors and Collaborators
University of Toronto
Investigators
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Principal Investigator: Rupert Kaul, MD/PhD University of Toronto

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Responsible Party: Rupert Kaul, Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT02527941     History of Changes
Other Study ID Numbers: UTorontoBV
First Posted: August 19, 2015    Key Record Dates
Last Update Posted: February 10, 2016
Last Verified: February 2016

Keywords provided by Rupert Kaul, University of Toronto:
Genital immunology
HIV susceptibility
Microbiome
Bacterial vaginosis
Virus entry assay

Additional relevant MeSH terms:
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Vaginitis
Metronidazole
HIV Infections
Disease Susceptibility
Vaginal Diseases
Vaginosis, Bacterial
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Disease Attributes
Pathologic Processes
Genital Diseases, Female
Bacterial Infections
Anti-Infective Agents
Anti-Bacterial Agents
Antiprotozoal Agents
Antiparasitic Agents