Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction (MoVe)

Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction Reveal Common Signalling Pathways Relevant for Disease Progression and Recovery

Patients with obstructive or neurogenic lower urinary tract disease will be invited to participate. Upon agreement they will undergo an assessment of bladder function (questionnaires) and bladder biopsies at 2 time-points. Bladder biopsies will be evaluated for molecular changes in the laboratory and compared to the functional findings.By uncovering the molecular similarities and differences between BLUTD and NLUTD, the investigators will elucidate some of the causative factors in the development of these disorders and highlight the impact of myogenic and neurogenic components postulated to be involved. The project involves close collaboration between clinical and basic research.

Study Overview

• Status: Completed
• Conditions: Disorder of the Lower Urinary Tract
• Intervention / Treatment: Procedure: Bladder biopsy; Procedure: Urodynamic study

Detailed Description

Lower urinary tract dysfunction (LUTD) has multiple causes including bladder outlet obstruction (BOO) as a result of benign prostatic hyperplasia (BPH) and neurological diseases including spinal cord injury (SCI). Manifestations of LUTD include storage symptoms such as increased daytime frequency, nocturia, urgency and urinary incontinence and voiding symptoms such as slow stream, hesitancy and incomplete emptying. The consequences of both BOO-induced (BLUTD) and neurogenic LUTD (NLUTD), leading to functional entities including the low compliance high pressure bladder as well as the acontractile high volume low pressure bladder, are believed to share some pathogenetic mechanisms.

In a previous project, the investigators have established micro ribonucleic acid (miRNA) and messenger ribonucleic acid (mRNA) expression profiles of several urodynamically defined states of BLUTD. In this follow-up project, the investigators propose to extend these studies, undertaking a comparative miRNA and RNA profiling of BLUTD and NLUTD, and investigate the dynamic alteration of microRNA expression in different functional manifestations of disease. The investigators propose to validate primary gene targets of miRNAs differentially expressed in urodynamically defined states of BLUTD and identify signaling pathways, activated during the progression from hypertrophy to decompensation. Monitoring the reversal of changes in miRNA expression after relief of obstruction and restoration of normal bladder function will help delineate the key BOO-induced miRNAs with regulatory potential. Similarly, the dynamics of miRNA alteration, observed in SCI patients during the development and management of NLUTD should reveal the role of miRNA in gene expression regulation during neurogenic-induced organ remodelling.

By uncovering the molecular similarities and differences between BLUTD and NLUTD, the investigators will elucidate some of the causative factors in the development of these disorders and highlight the impact of myogenic and neurogenic components postulated to be involved. The project involves close collaboration between clinical and basic research, and combines the analysis of human biopsy material with in vitro cell-based assays, creating a comprehensive platform for the dissection of molecular mechanisms of LUTD. This project will keep the momentum of the investigators' previous research and contribute to the basic and applied studies into bladder remodeling. It is a logical continuation of their on-going studies of the role of miRNAs in LUT disorders but represents a novel direction of research and has high diagnostic and therapeutic potential.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • University Hospital Inselspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Controls: patients with cystoscopy for stone disease or microhematuria without bladder symptoms Patients with spinal cord injury or benign prostatic obstruction.

Description

Inclusion Criteria:

• Planned cystoscopy in anesthesia for upper tract stone treatment or microscopic hematuria evaluation (controls)
• Planned TURP (transurethral prostate resection) (BLUTD)
• Spinal cord injury (in last 6 weeks) (NLUTD)
• Prior urodynamic study
• Informed consent

Exclusion Criteria:

• Age < 18 years old
• Pregnancy
• Urinary tract infection
• History of or current genitourinary tuberculosis, bladder malignancy, radiotherapy.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; No lower urinary tract symptoms undergoing cystoscopy in anesthesia for stone treatment or microhematuria assessment.	Procedure: Bladder biopsy; Small biopsy of the bladder is taken with cold-cup tongs.
Spinal cord injury/acontractile; Patients with traumatic spinal cord injury (SCI) with no (neither spontaneous nor provoked) detrusor activity during the filling phase of urodynamics. Bladder biopsy 6 weeks after trauma 6 months later urodynamic study and bladder biopsy	Procedure: Bladder biopsy; Small biopsy of the bladder is taken with cold-cup tongs.; Procedure: Urodynamic study; Assessment of bladder function through intravesical and intrabdominal pressure measurements according to International Continence Society standards.
Spinal cord injury/Detrusor overactivity; SCI patients with proven detrusor (urodynamics) overactivity during the filling phase. Bladder biopsy 6 weeks after trauma 6 months later urodynamic study and bladder biopsy	Procedure: Bladder biopsy; Small biopsy of the bladder is taken with cold-cup tongs.; Procedure: Urodynamic study; Assessment of bladder function through intravesical and intrabdominal pressure measurements according to International Continence Society standards.
Prostatic obstruction/acontractile; Low flow to no flow, no measurable detrusor activity on urodynamic evaluation, cystoscopy in line with obstruction. Bladder biopsy at TURP (transurethral resection prostate) 3 months later urodynamic study and bladder biopsy	Procedure: Bladder biopsy; Small biopsy of the bladder is taken with cold-cup tongs.; Procedure: Urodynamic study; Assessment of bladder function through intravesical and intrabdominal pressure measurements according to International Continence Society standards.
Prostatic obstruction/ obstructed; Obstruction according to Schäfer nomogram on urodynamic evaluation. Bladder biopsy at TURP 3 months later urodynamic study and bladder biopsy	Procedure: Bladder biopsy; Small biopsy of the bladder is taken with cold-cup tongs.; Procedure: Urodynamic study; Assessment of bladder function through intravesical and intrabdominal pressure measurements according to International Continence Society standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establishment of mRNA targets and pathways defining a disease state and/or potentially amendable to pharmacological evaluation.	Next generation sequencing of bladder wall tissue to determine changes in mRNAs and their targets and pathways	8 years

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Swiss National Science Foundation; Balgrist University Hospital
• Investigators: Principal Investigator: Fiona C Burkhard, MD, University Hospital Inselspital, Berne; Principal Investigator: Jürgen Pannek, MD, Swiss Paraplegic Center Nottwil

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 7, 2015
• First Posted (Estimate): April 8, 2015

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Bladder; benign prostatic obstruction; neurogenic lower urinary tract dysfunction
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Urinary Bladder, Neurogenic
• Other Study ID Numbers: 331/2014