Clinical trial NCT02410876: Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction
Official title: Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction Reveal Common Signalling Pathways Relevant for Disease Progression and Recovery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Disorder of the Lower Urinary Tract
Keywords: Bladder
neurogenic lower urinary tract dysfunction
benign prostatic obstruction
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: Balgrist University Hospital
First posted: 2015-04-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Establishment of mRNA targets and pathways defining a disease state and/or potentially amendable to pharmacological evaluation.
timeFrame: 8 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital Inselspital
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Fiona C Burkhard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swiss paraplegic center Nottwil
name: Jürgen Pannek, MD
role: PRINCIPAL_INVESTIGATOR
References: