Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02410876 |
Other study ID # |
331/2014 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
June 2015 |
Est. completion date |
December 31, 2020 |
Study information
Verified date |
April 2021 |
Source |
University Hospital Inselspital, Berne |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial 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.
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.