Vulvovaginal Candidiasis in Canadian Females (THRIVE-yeast)

Prospective Studies of Vaginal Yeast and Microbiome Related to Vulvovaginal Candidiasis in Canadian Females

Vulvovaginal candidiasis (VVC; colloquially referred to as a 'yeast infection') is a prevalent mucosal infection caused by Candida spp. that affects ~75% of women at least once in their life. VVC usually responds well to treatment, yet a small but significant fraction of women experience recurrent yeast infections even with weekly treatment. A further complication in understanding the causes of recurrent infections is that approximately one in five females have vaginal yeast present without any symptoms at any given point. The link between fungi, other microbes in the vagina ("microbiome"), and the human immune system remain poorly understood in the switch from having yeast present in the vagina without any symptoms and symptomatic yeast infections. Fungi also compose a normal component of the microbiome at other sites in the body (e.g., oral, skin, gastrointestinal tract, rectum) where they may serve as a source of re-infection following treatment.

In addition to the commonly prescribed 'first choice' antifungal drug fluconazole, a second-line treatment, boric acid, has shown promise in the literature and has been used locally with success at increasing the time between recurrent infections. A drawback of this therapy, however, is cost, as it is a compounded medication, and patients have to pay out of pocket. The purpose of this study is to understand how the yeast and bacterial microbial communities differ for females with recurrent infections from females with their first yeast infection and females with vaginal yeast present without any symptoms, and to track yeast diversity following treatment with either boric acid or fluconazole. The investigators hypothesize that they will identify multiple subpopulations of yeast at multiple anatomical body sites in females with VVC and recurrent VVC. They anticipate finding evidence for recurrent infection from secondary sites by linking genomic diversity of vaginal yeast strains during symptomatic infection to strains from other body sites. They hypothesize that yeast isolated from females with recurrent infections will exhibit different drug response phenotypes than yeast from females with asymptomatic vaginal yeast. They hypothesize that the vaginal microbiome of post-treatment patients treated with boric acid will differ from that of fluconazole. Combined, they hypothesize that post-treatment response will differ between the drugs, indicating that treatment specifics influence the vaginal environment.

Study Overview

• Status: Recruiting
• Conditions: Candidiasis, Vulvovaginal
• Intervention / Treatment: Drug: Boric Acid Supp,Vag; Drug: Fluconazole 150 mg

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Vanessa Poliquin, MD; Phone Number: 204-787-4796; Email: vpoliquin@hsc.mb.ca
• Study Contact Backup: Name: Vanessa HSC Women's Health Research Program, MD; Phone Number: 204-975-7723

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Recruiting
      • Health Science Centre (HSC)
      • Contact: Phone Number: 204-975-7723

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female
• Between ages of 18 and 50 years.

Exclusion Criteria:

• Currently pregnant
• Trying to get pregnant
• Have had a hysterectomy
• BV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Recurrent Infection Cohort - symptomatic; Participants with a history of recurrent vulvovaginal candidiasis infections who have an active symptomatic infection when they come to clinic	Drug: Boric Acid Supp,Vag; Treatment will be offered to participants if clinical exam and clinical samples are consistent with vulvovaginal candidiasis (VVC). Women that have had a prior documented VVC infection that has recurred on fluconazole will be treated with boric acid, 600 mg intravaginally at bedtime for 7 days.; Drug: Fluconazole 150 mg; Treatment will be offered to participants if clinical exam and clinical samples are consistent with vulvovaginal candidiasis (VVC). Females presenting with a suspected first-time yeast infection will be treated with fluconazole 150 mg orally.
No Intervention: Asymptomatic Cohort; Participants with no history of vulvovaginal candidiasis
No Intervention: Recurrent Infection Cohort - asymptomatic; Participants with a history of recurrent vulvovaginal candidiasis infections who do not have an active symptomatic infection when they come to clinic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fungal Diversity	Use culture-based methods, flow cytometry, and genome sequencing to: Test how genotypic diversity, genetic relatedness, and drug resistance and tolerance changes in the fungal population from the assumed first-time infection cohort and recurrent infection cohort participants before and after treatment with either fluconazole or boric acid.; How the vaginal fungal population diversity differs between symptomatic and asymptomatic participants.; Test how the vaginal fungal isolates in participants with VVC are related to rectal, oral, and skin fungal isolates.	One month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial Diversity	Using 16S-rRNA sequencing and meta-proteomic to characterize the bacterial diversity changes pre-and post- drug treatment for VVC.	One month
Host Functional Changes	Host proteome of the vaginal samples will be assessed using proteomics to determine any underlying inflammatory or barrier pathways that associate with treatment of VVC.	One month

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Manitoba Medical Service Foundation; Research Manitoba
• Investigators: Principal Investigator: Aleeza Gerstein, PhD, University of Manitoba

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2021
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Vaginal Diseases; Vulvar Diseases; Vaginitis; Vulvitis; Vulvovaginitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Candidiasis; Candidiasis, Vulvovaginal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: B2021:026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified proteomics and microbiome data collected will be placed into a freely available data repository after peer review of publications via Genbank. The proteomic expression data shall be made available by depositing the raw, untransformed and normalized counts on our servers. Whole genome sequencing data will be made available on the National Center for Biotechnology Information (NCBI) short reads archive. Any other functional data shall be made available with the journal publications in the text, or as supplementary material at the publisher's online website, or in data repositories (e.g., Dryad, https://datadryad.org).
• IPD Sharing Time Frame: Following publication in peer-reviewed journal articles, data available indefinitely.
• IPD Sharing Access Criteria: Following publication, external collaborators wishing to make use of THRIVE-yeast data must first contact the PI and submit a written proposal to request access to de-identified data. The PI will consult with University of Manitoba Office of Research Services to create a Data Sharing Transfer Agreement.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes