The Female Microbiome in Patients Undergoing Bladder Instillation Therapy

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.

Study Overview

• Status: Completed
• Conditions: Microbial Colonization; Interstitial Cystitis; Bladder Pain Syndrome
• Intervention / Treatment: Drug: Heparin & Alkalinized Lidocaine Bladder Instillation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Heparin & Alkalinized Lidocaine Bladder Instillation; 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; Bladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Walter Reed National Military Medical Center
• Collaborators: US Army Medical Research Institute of Infectious Diseases
• Investigators: Principal Investigator: Eva K Welch, MD MS, Walter Reed National Military Medical Center

Publications and helpful links

General Publications

• Wolfe AJ, Toh E, Shibata N, Rong R, Kenton K, Fitzgerald M, Mueller ER, Schreckenberger P, Dong Q, Nelson DE, Brubaker L. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012 Apr;50(4):1376-83. doi: 10.1128/JCM.05852-11. Epub 2012 Jan 25.
• Pearce MM, Zilliox MJ, Rosenfeld AB, Thomas-White KJ, Richter HE, Nager CW, Visco AG, Nygaard IE, Barber MD, Schaffer J, Moalli P, Sung VW, Smith AL, Rogers R, Nolen TL, Wallace D, Meikle SF, Gai X, Wolfe AJ, Brubaker L; Pelvic Floor Disorders Network. The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol. 2015 Sep;213(3):347.e1-11. doi: 10.1016/j.ajog.2015.07.009. Epub 2015 Jul 23.
• Abernethy MG, Rosenfeld A, White JR, Mueller MG, Lewicky-Gaupp C, Kenton K. Urinary Microbiome and Cytokine Levels in Women With Interstitial Cystitis. Obstet Gynecol. 2017 Mar;129(3):500-506. doi: 10.1097/AOG.0000000000001892.
• Meriwether KV, Lei Z, Singh R, Gaskins J, Hobson DTG, Jala V. The Vaginal and Urinary Microbiomes in Premenopausal Women With Interstitial Cystitis/Bladder Pain Syndrome as Compared to Unaffected Controls: A Pilot Cross-Sectional Study. Front Cell Infect Microbiol. 2019 Apr 8;9:92. doi: 10.3389/fcimb.2019.00092. eCollection 2019.
• Nickel JC, Stephens-Shields AJ, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Henderson JP, Sen B, Krol JE, Ehrlich GD; MAPP Research Network. A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network. J Clin Med. 2019 Mar 26;8(3):415. doi: 10.3390/jcm8030415.
• Nickel JC, Stephens A, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Ehrlich GD; MAPP Research Network. Assessment of the Lower Urinary Tract Microbiota during Symptom Flare in Women with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study. J Urol. 2016 Feb;195(2):356-62. doi: 10.1016/j.juro.2015.09.075. Epub 2015 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis; Infections; Communicable Diseases; Cystitis, Interstitial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Fibrinolytic Agents; Fibrin Modulating Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Anticoagulants; Lidocaine; Heparin
• Other Study ID Numbers: WRNMMC-EDO-2021-0728

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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