The Female Microbiome in Patients Undergoing Bladder Instillation Therapy

Study Overview
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Brief Summary
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The underlying pathophysiology for BPS/IC is currently an active area of research. There is speculation that there may be alteration in the bladder and vaginal microbiome that contributes to the symptomatology of BPS/IC, however existing literature is limited and contradictory. Nickel et al (2015) studied the bladder microbiota in women with IC/BPS during a flare versus nonflare. The study collected initial stream and midstream urine specimens and detected overall, there was no significant differences in the species composition. However, a greater prevalence of fungi (Candida and Saccharomyces) was seen in the flare group (15.7%) versus the non-flare group (3.9%) midstream urine specimens. Pearce et al (2015) sought to characterize the urinary microbiome via catheterized specimens from women with urgency urinary incontinence, a condition that can present similarly as IC/BPS. The study found that more than half of the patients were sequence positive, most commonly for Lactobacillus (45%) or Gardnerella (17%), with 25% made up of various other bacteria. In contrast, Abernethy et al (2017) showed via catheterized urine specimens from patients with IC/BPS that the urinary microbiome is less diverse and less likely to contain Lactobacillus species. There have been two recent studies investigating the female urinary microbiome in patients with IC/BPS. Nickel et al (2019) found no differences in species composition between urine from patients with IC/BPS versus controls. Meriwether et al (2019) reported similar findings, and additionally found no differences when comparing the vaginal bacterial microbiome in patients with IC/BPS versus controls. However, in evaluating the bladder microbiome, both studies utilized uncatheterized urine specimens. Wolfe et al (2012) showed microbiome differences between clean-catch and catheterized urine specimens, therefore vaginal contamination in both studies cannot be ruled out.

Detailed Description
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This study uses samples collected under an interventional study and consented for use in future research - this study is use of those samples under the future research provision, and this study was deemed to meet exempt category 4.

Official Title
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The Female Microbiome in Patients Undergoing Bladder Instillation Therapy

Conditions
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Interstitial Cystitis, Bladder Pain Syndrome, Microbial Colonization

Intervention / Treatment
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* Drug: Heparin & Alkalinized Lidocaine Bladder Instillation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who previously or will be undergoing bladder instillation therapy for treatment of IC/BPS and whom had or will have urine/vaginal specimens collected at the beginning and between 4-6th instillations. Exclusion Criteria: Patients not meeting inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Heparin & Alkalinized Lidocaine Bladder Instillation<br>Six weekly bladder instillations, each instillation consisting of 40,000 IU Heparin, 200mg lidocaine, 2ml 8.4% sodium bicarbonate, sterile water for a total volume 50 milliliters (mL). | Drug: Heparin & Alkalinized Lidocaine Bladder Instillation<br>* Bladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the female microbiome as measured by bacterial ribosomal RNA sequencing in patients with BPS/IC at baseline and during bladder instillation therapy |  | Baseline, 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and O'Leary-Sant questionnaire scores | Consists of O'Leary-Sant Symptom and Problem Index. Total score 0-36, with higher scores indicating worse symptoms | Baseline, 4-6 weeks | 
| Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Female Sexual Function Index (pain) questionnaire scores | Total score 0-6, with higher scores indicating worse symptoms | Baseline, 4-6 weeks | 
| Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Female Sexual Distress-Revised Inventory questionnaire scores | FSDS-R evaluates distress associated with inadequate/impaired sexual function. Total score 0-52, with higher scores indicating worse symptoms | Baseline, 4-6 weeks | 
| Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Short Form 12 questionnaire scores | SF-12 is a general health questionnaire that evaluates quality of life measures, divided into mental and physical component scores. Higher scores associated with better symptoms. | Baseline, 4-6 weeks | 
| Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Visual Analog Scale questionnaire scores | Scale of 0-10 (0= no pain, 10 = worst pain) | Baseline, 4-6 weeks | 
| Characterization of bacterial species present as measured by bacterial ribosomal RNA sequencing in the vaginal and urinary microbiome |  | Baseline, 4-6 weeks | 
| Characterization of bacterial species diversity as measured by bacterial ribosomal RNA sequencing in the vaginal and urinary microbiome |  | Baseline, 4-6 weeks |