Clinical trial NCT06649201: Vulvovaginal Graft-versus-Host Disease: Diagnosis and Microbiome Evaluation
Official title: Vulvovaginal Graft-versus-Host Disease: Diagnosis and Microbiome Evaluation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Graft Vs Host Disease
Vulvovaginal Signs and Symptoms
Keywords: Allogeneic Hematopoietic Cell Transplantation
Vaginal Microbiome
GVHD
HCT
Vulvovaginal GVHD
Vulvovaginal graft-versus-host disease
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2024-10-18
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female participants undergoing allogenic HCT will be recruited from the Blood and Marrow Transplant Program at the Cleveland Clinic.

Brief summary: The goal of this observational study is to investigate the development of vulvovaginal graft-versus-host- disease (GVHD), an under-reported and under-recognized manifestation of chronic GVHD. This study aims to characterize the vaginal microbiome in participants undergoing allogeneic hematopoietic cell transplantation (HCT). The main questions it aims to answer are:

* Is the vaginal microbiome altered during allogeneic HCT?
* What changes may help researchers understand the development of vulvovaginal GVHD?

Participants will be asked to undergo an assessment of vulvovaginal symptoms through a vulvovaginal symptom questionnaire once pre-transplant, 6 months post-transplant, and twelve12 months post- transplant. Participants will also be asked to undergo a vaginal microbiome (collection of bacteria, fungi, and viruses that live on our bodies) evaluation through a vaginal exam performed by a gynecologist with collection of vaginal samples once pre-transplant and again six months post-treatment and twelve months post-transplant. If a participant develops symptoms of vulvovaginal GVHD at any point in time during the post-transplant follow up, the participant may partake in additional vaginal exams to diagnose GVHD at the time of symptom onset.

Detailed description: Recent advances in technologies including high throughput metagenomic 16S rRNA gene sequencing have revealed a larger, more complex picture of the bacterial diversity in the genital tract and unique microbial communities not previously recognized among the known vaginal flora categories. Little is known about how the vaginal microbiome protects the female genital tract or other roles it may have, including interacting with the microbiota of other body sites and subsequent inflammatory responses. Alteration of vaginal flora may play a part in the pathogenesis of diseases by modulating immunity or increasing the growth of pathogenic strains. Recent research has been conducted regarding changes in the vaginal microbiome during various infectious and inflammatory states such as bacterial vaginosis, pelvic inflammatory disease, sexually transmitted infectious, and pregnancy. However, the vaginal microbiome during allogeneic HCT and development of genital GVHD has yet to be examined. Thus, the role of the vaginal microbiome in the development of genital GVHD is a critical area of study.

Eligibility criteria: Inclusion Criteria:

* Female participants planning to undergo allogeneic HCT for any disease indication, OR, female participants who have already received HCT and have developed vulvovaginal GVHD during their post-transplant follow-up period
* All conditioning regimens (myeloablative or reduced intensity) will be included.
* All donor sources (HLA matched/mismatched related, unrelated, umbilical cord, haploidentical) will be included.
* All graft sources (bone marrow or peripheral blood stem cells) will be included.
* All GVHD prophylaxis regimens will be included.
* Aged 18-70.
* English speaking and able to sign written informed consent.
* Participants agree to a vaginal gynecologic exam.
* Co-enrollment on other clinical trials will be allowed.

Exclusion Criteria:

* Participants who decline or unable to undergo vaginal gynecologic exam due to any discomfort or pain.
* Any concurrent medical, psychiatric or other illness in which the provider believes the participants may not be able to comply with study assessments.
* Participants with a current diagnosis of a sexually transmitted infection (STI) (Herpes Simplex Virus, Gonorrhea, Chlamydia, Trichomonas,) or a history of previously untreated STI which may incite inflammation that will impact the microbiome.
* Participants with a history of lichen sclerosis, lichen planus, pre-transplant.
* Participants with a history or current diagnosis of vaginal or vulvar malignancy.

Primary outcomes:
measure: Characterize the vaginal microbiome profile of female participants undergoing allogeneic HCT
timeFrame: Up to twelve months post-transplant
measure: Characterize the change in vaginal microbiome profile of female participants undergoing allogeneic HCT
timeFrame: Up to twelve months post-transplant
measure: Incidence of vulvovaginal GVHD
timeFrame: Up to twelve months post-transplant
Secondary outcomes:
measure: Characterize the differences in vaginal microbiome between participants who develop vulvovaginal GVHS versus those who do not
timeFrame: Up to twelve months post-transplant
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Betty K Hamilton, MD
role: PRINCIPAL_INVESTIGATOR
References: