Interstitial CystitisPhase 2NCT05414305
The Female Microbiome in Patients Undergoing Bladder Instillation Therapy
A Phase 2 study testing Heparin & Alkalinized Lidocaine Bladder Instillation in people with Interstitial Cystitis and Bladder Pain Syndrome, run by Walter Reed National Military Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Interstitial Cystitis, Bladder Pain Syndrome, Microbial Colonization
- What is being tested?
- Heparin & Alkalinized Lidocaine Bladder Instillation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 1 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Patients not meeting inclusion criteria
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
About this study
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.
Read the 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.
- Being tested
- Heparin & Alkalinized Lidocaine Bladder Instillation
- Medical subject headings
- Cystitis, Interstitial, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heparin & Alkalinized Lidocaine Bladder InstillationDrug
Bladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void
| Study group | Role | What they receive |
|---|---|---|
| Heparin & Alkalinized Lidocaine Bladder Instillation | Other | 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). Receives: Drug: Heparin & Alkalinized Lidocaine Bladder Instillation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of the female microbiome as measured by bacterial ribosomal RNA sequencing in patients with BPS/IC at baseline and during bladder instillation therapy
Measured: Baseline, 4-6 weeks
Secondary outcomes (7)
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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)
Measured: Baseline, 4-6 weeks
Characterization of bacterial species present as measured by bacterial ribosomal RNA sequencing in the vaginal and urinary microbiome
Measured: Baseline, 4-6 weeks
Characterization of bacterial species diversity as measured by bacterial ribosomal RNA sequencing in the vaginal and urinary microbiome
Measured: Baseline, 4-6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start1 Oct 2020
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Interstitial CystitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Walter Reed National Military Medical Center
- Sponsor type
- US federal agency
- Collaborators
- US Army Medical Research Institute of Infectious Diseases
- Responsible party
- Sponsor
- Investigators
- Eva K Welch, MD MS, Principal investigator, Walter Reed National Military Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05414305
- Sponsor's protocol ID
- WRNMMC-EDO-2021-0728
- Status last verified
- Aug 2024
- First submitted
- 26 May 2022
- Last updated
- 14 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 22278835Pearce 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.
PubMed 26210757Abernethy 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.
PubMed 28178051Meriwether 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.
PubMed 31024861Nickel 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.
PubMed 30917614Nickel 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.
PubMed 26410734
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Female Microbiome in Patients Undergoing Bladder Instillation Therapy
- ClinicalTrials.gov ID
- NCT05414305
- Acronym / sponsor ID
- WRNMMC-EDO-2021-0728
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Walter Reed National Military Medical CenterUS federal agency
- Collaborators
- US Army Medical Research Institute of Infectious Diseases
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 10 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Heparin & Alkalinized Lidocaine Bladder Instillation | Other | Drug: Heparin & Alkalinized Lidocaine Bladder InstillationSix 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Patients not meeting inclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Heparin & Alkalinized Lidocaine Bladder InstillationBladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void | Drug | Heparin & Alkalinized Lidocaine Bladder Instillation |
Primary outcome
Change of the female microbiome as measured by bacterial ribosomal RNA sequencing in patients with BPS/IC at baseline and during bladder instillation therapy
Time frame: Baseline, 4-6 weeks
7 secondary outcomes
Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and O'Leary-Sant questionnaire scores
Time frame: Baseline, 4-6 weeks
Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Female Sexual Function Index (pain) questionnaire scores
Time frame: Baseline, 4-6 weeks
Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Female Sexual Distress-Revised Inventory questionnaire scores
Time frame: Baseline, 4-6 weeks
Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Short Form 12 questionnaire scores
Time frame: Baseline, 4-6 weeks
Correlation of female microbiome as measured by bacterial ribosomal RNA sequencing and Visual Analog Scale questionnaire scores
Time frame: Baseline, 4-6 weeks
Characterization of bacterial species present as measured by bacterial ribosomal RNA sequencing in the vaginal and urinary microbiome
Time frame: Baseline, 4-6 weeks
Characterization of bacterial species diversity as measured by bacterial ribosomal RNA sequencing in the vaginal and urinary microbiome
Time frame: Baseline, 4-6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2024.
- Background: PubMed 22278835Wolfe 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.
- Background: PubMed 26210757Pearce 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.
- Background: PubMed 28178051Abernethy 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.
- Background: PubMed 31024861Meriwether 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.
- Background: PubMed 30917614Nickel 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.
- Background: PubMed 26410734Nickel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva K Welch, MD MS principal investigator
Walter Reed National Military Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Heparin & Alkalinized Lidocaine Bladder Instillation in people with Interstitial Cystitis and Bladder Pain Syndrome, run by Walter Reed National Military Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of the female microbiome as measured by bacterial ribosomal RNA sequencing in patients with BPS/IC at baseline and during bladder instillation therapy (time frame: Baseline, 4-6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05414305, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2024.