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Assessment of Urinary Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) Technology in the Evaluation and Management of Females With Chronic Bladder Pain and Cystitis-like Symptoms

Primary Purpose

Interstitial Cystitis, Bladder Pain Syndrome

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Polymerase Chain Reaction and Next-Generation DNA Sequencing

About this trial

This is an interventional diagnostic trial for Interstitial Cystitis focused on measuring BPS, IC, NGS, PCR

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Subjects are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in this protocol.
Symptomatic subjects with BPS (NIH/NIDDK/MAPP definition) with perceived bladder pain +/- urinary storage symptoms) or symptomatic patients with CCS (chronic UTI definition based on modified ACSS with dysuria)
Subjects with previous failure of standard urine culture directed therapy approach, eg. antibiotic treatment based on previous urine culture results (positive, sterile, or nebulous) failed to provide appreciable clinical benefit.
Subjects who have experienced a minimum of 3 months of continuous symptoms
Subjects who have a minimum average daily bladder pain score of ≥ 3 on a 0-10 NRS scale in the past 3 months
Subjects with no antibiotic therapy for the previous 2 weeks
Subjects with no UTI supplements including cranberry, d-mannose, high dose vitamin C and Lactobacillus probiotics for the previous 2 weeks.

Exclusion Criteria: Subjects will be excluded from participating in this study if they meet any of the following criteria:

Subjects with any of the following confounding conditions: bladder stones, lower ureteric stones, vaginal candidiasis, urethral diverticulum, urinary retention (≥ 300 mL), overactive bladder (ie, urinary urgency secondary to urinary incontinence), or any other condition/disease, which, in the opinion of the investigator, could compromise patient safety or confound the collection or interpretation of study results.
Subjects who are pregnant or planning a pregnancy during the study period
Subjects with a history of previous urinary diversion procedure with or without bladder removal or bladder augmentation.
Subjects with a history of bladder cystoscopy only within 1 month or cystoscopy with bladder biopsy, hydrodistension, fulguration or triamcinolone injection or treatment of Hunner ulcer performed within 3 months prior to Screening.
Subjects with a medical history of carcinoma and carcinoma in situ of the bladder, urethral cancer, or pelvic radiotherapy.
Subjects with a neurogenic bladder (due to spinal cord injury, stroke, Parkinson's disease, multiple sclerosis, spina bifida, or diabetic cystopathy).
Subjects with genital herpes active within 3 months prior to screening.
Subjects with a history of gross (visible) hematuria within 1 year prior to screening that has not been evaluated.
Subjects who have had major surgery within the past 3 months or has surgery planned during the study period
Subjects with a history of alcohol and/or drug abuse that in the investigator's opinion could interfere with the study evaluations or the patient's safety.
Subjects catheterized in the past month
Subjects that have received antibiotic treatment based on MicroGenDX's NGS results in the prior 12 months
Subjects with indwelling ureteral stents
Subjects that have received a bladder instillation within the last 4 weeks

Sites / Locations

UCLA Center for Women's Pelvic HealthRecruiting
The University of California San Diego HealthRecruiting
Cooper University Health CareRecruiting
Wake Forest University Baptist Medical Center Urology

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single arm

Arm Description

All subject's samples will undergo the same diagnostic test utilizing Polymerase Chain Reaction and Next-Generation DNA Sequencing

Outcomes

Primary Outcome Measures

Effectiveness of PCR/NGS directed antimicrobial therapy assessed by the Global Response Assessment (GRA)

GRA is a 7-point descriptive scale in which subjects self-report that degree that their symptoms improved or worsened compared to baseline. The answers available for the subject includes markedly improved, moderately improved, mildly improved, no change, mildly worse, moderately worse, markedly worse. A responder is a subject who reports that compared to baseline their symptoms are moderately or markedly improved. The primary analysis will determine the proportion of subjects who are responders at the efficacy visit.

Secondary Outcome Measures

Safety of PCR/NGS directed antimicrobial therapy by measuring the incidence of Treatment-Emergent Adverse Events by the SAE questionnaire

Determine the safety of employing a PCR/NGS directed antimicrobial therapy strategy in female subjects with BPS and CCS.

concordance

Evaluate concordance of culture results with PCR/NGS findings in this population of women.

Type of sample comparison

Compare the microbiome of midstream and catheterized urine specimens of symptomatic female subjects with BPS and CCS.

Stratification comparison

Compare urinary microbiome of symptomatic population of women stratified based on PCR/NGS positive and PCR/NGS negative subgroups, positive/negative cultures, and BPS and CCS.

Full Information

NCT ID

NCT05276466

First Posted

November 4, 2021

Last Updated

March 13, 2023

Sponsor

MicroGenDX

1. Study Identification

Unique Protocol Identification Number

NCT05276466

Brief Title

Assessment of Urinary Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) Technology in the Evaluation and Management of Females With Chronic Bladder Pain and Cystitis-like Symptoms

Official Title

Assessment of Urinary Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) Technology in the Evaluation and Management of Females With Chronic Bladder Pain and Cystitis-like Symptoms

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 1, 2022 (Actual)

Primary Completion Date

November 15, 2023 (Anticipated)

Study Completion Date

December 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MicroGenDX

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Real-world clinical practice multicenter study to determine the clinical implications of employing PCR/NGS technology to identify and treat potential urinary pathogens in female participants identified with bladder pain and/or cystitis-like symptoms.

Detailed Description

This is a real-world clinical practice multicenter study to determine the clinical implications of employing PCR/NGS technology to identify and treat potential urinary pathogens in female patients identified with BPS and/or CCS symptoms. Eligible subjects will undergo a baseline/screening visit at which time the following will be collected: demographics/history, physical examination, Numerical Rating Scale (NRS) pain (average and maximum), Female Genito-Urinary Pain Index (F-GUPI), Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index (ICSI/ICPI), Acute Cystitis Symptom Score (ACSS), and the Short Form -12.v2 Quality of Life Questionnaire (SF-12). MSU and catheterized urine specimens will be collected for urinalysis (UA), standard culture, and PCR/NGS. Subjects will be stratified based on BPS (NIDDK MAPP criteria) or CCS (based on ACSS criteria) symptoms. Uropathogens detected on PCR/NGS catheterized specimens will be treated with 10 days of PCR/NGS directed antibiotic therapy which will be recommended by a centralized infectious disease consultant. If there are no uropathogenic bacteria in the catheter specimen, the MSU specimen will be used if positive. Prescribing physicians will adjust those recommendations (choice of antibiotic as well as duration of therapy) based on individual patient's history of antibiotic therapy and known allergies and sensitivities. Subjects with negative PCR/NGS findings for potential uropathogens will be treated with 10 days of empiric antibiotic therapy chosen by the investigator from this list b: 1. Trimethoprim sulfamethoxazole, 2. Macrocrystalline nitrofurantoin, 3. Fosfomycin, and 4. Investigator choice. More than one antibiotic may be prescribed if two or more uropathogens are identified. At the discretion of the treating physician with the consent and shared decision making with the patient, a decision may be made to continue antibiotic therapy beyond 10 days if the patient subjectively believes she is responding. In this study, all subjects will be offered antibiotic therapy, either NGS directed or empiric. Fourteen days after beginning antibiotics, the Subjective Global Assessment (SGA), compliance and safety will be determined via phone call. A clinic visit will be scheduled for 14 days after finishing antibiotics for repeat evaluation of symptoms (NRS pain, F-GUPI, ICSI/ICPI, ACSS, SF-12, SGA) and safety. A MSU urine specimen will be collected from all subjects and submitted for PCR/NGS analysis. Subjects who were PCR/NGS negative and failed empiric therapy will be notified that they likely do not have an infection. Primary analyses will be based on the responder rate (SGA responder rate will be the primary efficacy parameter), symptom change based on the other questionnaires, and safety in BPS/CCS subjects treated with PCR/NGS as well as those treated with empiric therapy. A 40% SGA responder rate, where a responder is defined as markedly or moderately improved on the GRA 7-point scale, will be considered a clinically significant impact. A follow-up visit 4 weeks later will collect similar data as collected at the efficacy visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Interstitial Cystitis, Bladder Pain Syndrome

Keywords

BPS, IC, NGS, PCR

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Single group assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single arm

Arm Type

Other

Arm Description

All subject's samples will undergo the same diagnostic test utilizing Polymerase Chain Reaction and Next-Generation DNA Sequencing

Intervention Type

Diagnostic Test

Intervention Name(s)

Polymerase Chain Reaction and Next-Generation DNA Sequencing

Intervention Description

The qPCR Rapid Screening Panel is a quantitative real-time PCR test for bacteria and fungi. Next-Generation DNA Sequencing is the Comprehensive Sequencing test will detect virtually all microbial organisms and fungal pathogens that may be present in patient specimens.

Primary Outcome Measure Information:

Title

Effectiveness of PCR/NGS directed antimicrobial therapy assessed by the Global Response Assessment (GRA)

Description

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Safety of PCR/NGS directed antimicrobial therapy by measuring the incidence of Treatment-Emergent Adverse Events by the SAE questionnaire

Description

Determine the safety of employing a PCR/NGS directed antimicrobial therapy strategy in female subjects with BPS and CCS.

Time Frame

1 year

Title

concordance

Description

Evaluate concordance of culture results with PCR/NGS findings in this population of women.

Time Frame

1 year

Title

Type of sample comparison

Description

Compare the microbiome of midstream and catheterized urine specimens of symptomatic female subjects with BPS and CCS.

Time Frame

1 year

Title

Stratification comparison

Description

Compare urinary microbiome of symptomatic population of women stratified based on PCR/NGS positive and PCR/NGS negative subgroups, positive/negative cultures, and BPS and CCS.

Time Frame

1 year

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects may be included in the study if they have bladder and/or urethral pain and lower urinary tract storage symptoms and only if they meet all of the following criteria at screening/baseline. Subjects are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in this protocol. Symptomatic subjects with BPS (NIH/NIDDK/MAPP definition) with perceived bladder pain +/- urinary storage symptoms) or symptomatic patients with CCS (chronic UTI definition based on modified ACSS with dysuria) Subjects with previous failure of standard urine culture directed therapy approach, eg. antibiotic treatment based on previous urine culture results (positive, sterile, or nebulous) failed to provide appreciable clinical benefit. Subjects who have experienced a minimum of 3 months of continuous symptoms Subjects who have a minimum average daily bladder pain score of ≥ 3 on a 0-10 NRS scale in the past 3 months Subjects with no antibiotic therapy for the previous 2 weeks Subjects with no UTI supplements including cranberry, d-mannose, high dose vitamin C and Lactobacillus probiotics for the previous 2 weeks. Exclusion Criteria: Subjects will be excluded from participating in this study if they meet any of the following criteria: Subjects with any of the following confounding conditions: bladder stones, lower ureteric stones, vaginal candidiasis, urethral diverticulum, urinary retention (≥ 300 mL), overactive bladder (ie, urinary urgency secondary to urinary incontinence), or any other condition/disease, which, in the opinion of the investigator, could compromise patient safety or confound the collection or interpretation of study results. Subjects who are pregnant or planning a pregnancy during the study period Subjects with a history of previous urinary diversion procedure with or without bladder removal or bladder augmentation. Subjects with a history of bladder cystoscopy only within 1 month or cystoscopy with bladder biopsy, hydrodistension, fulguration or triamcinolone injection or treatment of Hunner ulcer performed within 3 months prior to Screening. Subjects undergoing active treatment for cancer - urologic (eg bladder) or other - with surgery, radiation or chemotherapy within previous 8 weeks of screening. Subjects with a neurogenic bladder (due to spinal cord injury, stroke, Parkinson's disease, multiple sclerosis, spina bifida, or diabetic cystopathy). Subjects with genital herpes active within 3 months prior to screening. Subjects with a history of gross (visible) hematuria within 1 year prior to screening that has not been evaluated. Subjects who have had major surgery within the past 3 months or has surgery planned during the study period Subjects with a history of alcohol and/or drug abuse that in the investigator's opinion could interfere with the study evaluations or the patient's safety. Subjects catheterized in the past month Subjects that have received antibiotic treatment based on MicroGenDX's NGS results in the prior 12 months Subjects with indwelling ureteral stents Subjects that have received a bladder instillation within the last 4 weeks

Facility Information:

Facility Name

UCLA Center for Women's Pelvic Health

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Crystal Cisneros

Phone

833-825-2974

CCisneros@mednet.ucla.edu

First Name & Middle Initial & Last Name & Degree

Anne L Ackerman, MD

Facility Name

The University of California San Diego Health

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Trisha Kanie

Phone

619-543-6544

tkanie@health.ucsd.edu

First Name & Middle Initial & Last Name & Degree

Jennifer Anger, MD

Facility Name

Cooper University Health Care

City

Camden

State/Province

New Jersey

ZIP/Postal Code

08103

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bhaven Murji

Phone

856-968-7547

murji-bhaven@cooperhealth.edu

First Name & Middle Initial & Last Name & Degree

Lioudmila Lipetskaia, MD

Facility Name

Wake Forest University Baptist Medical Center Urology

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

Individual Site Status

Completed

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Currently no plan to share individual data to other researchers.

Citations:

PubMed Identifier

21497847

Citation

Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM; Interstitial Cystitis Guidelines Panel of the American Urological Association Education and Research, Inc. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011 Jun;185(6):2162-70. doi: 10.1016/j.juro.2011.03.064. Epub 2011 Apr 16.

Results Reference

background

PubMed Identifier

21920661

Citation

Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, Wyndaele JJ. Contemporary management of the painful bladder: a systematic review. Eur Urol. 2012 Jan;61(1):29-53. doi: 10.1016/j.eururo.2011.07.069. Epub 2011 Sep 9.

Results Reference

background

PubMed Identifier

30917614

Citation

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.

Results Reference

background

PubMed Identifier

26410734

Citation

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.

Results Reference

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PubMed Identifier

33352734

Citation

Alidjanov JF, Naber KG, Pilatz A, Wagenlehner FM. Validation of the American English Acute Cystitis Symptom Score. Antibiotics (Basel). 2020 Dec 19;9(12):929. doi: 10.3390/antibiotics9120929.

Results Reference

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PubMed Identifier

9146003

Citation

O'Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology. 1997 May;49(5A Suppl):58-63. doi: 10.1016/s0090-4295(99)80333-1.

Results Reference

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Assessment of Urinary Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) Technology in the Evaluation and Management of Females With Chronic Bladder Pain and Cystitis-like Symptoms

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