The Role of microRNAs in Organ Remodeling in Lower Urinary Tract Dysfunction

NCT01482676 | Completed

• 1 other identifier: 146/05b
• Study Type: observational
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Urgency, frequency and incomplete emptying are the key symptoms of lower urinary tract dysfunction, including bladder pain syndrome/interstitial cystitis, and overactive bladder syndrome. Lower urinary tract dysfunction is associated with cellular stress, leading to changes in gene expression and consequent organ remodeling. MicroRNAs are small regulatory molecules, affecting protein synthesis. They are quickly winning recognition as potential therapeutic agents. The investigators will perform a comparative study of mRNAs changed in lower urinary tract dysfunction and address the role of differentially expressed miRNAs in regulation of the genes, important for bladder function. The experimental approach, combining the analysis of human biopsy material with the in vitro cell-based models, will allow the investigators to elucidate the effects of miRNAs on the expression of receptors, contractile proteins and tight junction proteins. Once the disease-induced miRNAs have been characterised and their target genes validated, it will be possible to influence their expression levels thus counter-acting their effects. The investigators' work addresses fundamental mechanisms of signal transduction in urothelium and smooth muscle during cellular stress caused by inflammation or bladder outlet obstruction, and its regulation in the diseased state. The investigators' findings will further the knowledge of the molecular mechanisms of lower urinary tract dysfunction and have implications for diagnosis and treatment. Additionally, they have relevance for other clinical conditions, where miRNAs are implicated.

Conditions

Prostatic Hyperplasia; Urinary Bladder Neck Obstruction; Cystitis, Interstitial

Outcome Measures

Primary Outcomes (1)

• Molecular traits of bladder dysfunction

  3 years

Secondary Outcomes (3)

• MiRNA expression profiling of individual groups

  3 years

• Protein expression profiling of individual groups

  3 years

• Functional differences between groups

  3 years

Study Arms (4)

1

controls (normal bladder function)

2

acontractile bladder

3

overactive bladder

4

bladder pain syndrome

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients Department of Urology, Inselspital Bern, Switzerland

You may qualify if:

• prostate hyperplasia
• bladder acontractility
• bladder pain
• age over 18 years old
• willingness to participate (informed concent)

You may not qualify if:

• Age ≤ 18 years old
• Pregnancy
• History of or current genito-urinary tuberculosis
• History of pelvic surgery in the last 6 months
• History of bladder malignancy, high grade dysplasia or carcinoma in situ
• sexually transmitted diseases (STD's)
• Bacteriuria

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Department of Urology, Bern University hospital

Bern, Canton of Bern, 3010, Switzerland

Location

Related Publications (4)

• Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009 Jan 23;136(2):215-33. doi: 10.1016/j.cell.2009.01.002.

  PMID: 19167326 BACKGROUND

• Cardozo LD, Van Kerrebroeck PE, Staskin DR. Considerations for the management of urgency symptoms in patients with overactive bladder syndrome. World J Urol. 2009 Dec;27(6):755-63. doi: 10.1007/s00345-009-0455-4.

  PMID: 19690868 BACKGROUND

• Donaldson MM, Thompson JR, Matthews RJ, Dallosso HM, McGrother CW; Leicestershire MRC Incontinence Study Group. The natural history of overactive bladder and stress urinary incontinence in older women in the community: a 3-year prospective cohort study. Neurourol Urodyn. 2006;25(7):709-16. doi: 10.1002/nau.20235.

  PMID: 16998862 BACKGROUND

• Keay S. Cell signaling in interstitial cystitis/painful bladder syndrome. Cell Signal. 2008 Dec;20(12):2174-9. doi: 10.1016/j.cellsig.2008.06.004. Epub 2008 Jun 19.

  PMID: 18602988 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Frozen cold-cut bladder biopsies preserved in RNAlater buffer or in SDS-PAGE sample buffer; PFA-fixed tissue, primary cultures of urothelium and smooth muscle

MeSH Terms

Conditions

Prostatic Hyperplasia; Urinary Bladder Neck Obstruction; Cystitis, Interstitial

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Urethral Obstruction; Urethral Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urinary Bladder Diseases; Cystitis

Study Officials

• Katia Monastyrskaya, PhD

  Department of Urology, Bern University hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 30, 2011
• Study Start: October 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 3, 2015

Record last verified: 2015-06

Locations

CH (1)