Proteomic Pattern in Female Stress Urinary Incontinence: a Pilot Study

March 13, 2024 updated by: Marianne Koch, Medical University of Vienna

Objective: The primary objective of the study is the comparison of protein concentrations between patients with stress urinary incontinence (SUI) and healthy controls.

Aim: This pilot study aims to determine a possible altered protein profile in women suffering from SUI, compared to healthy women and therefore to discriminate a potential protein biomarker for SUI.

Main outcome measure: mass spectrometric measuring of urinary proteomic secretome in diseased and healthy subjects (sequence coverage and number of identified proteins)

Trial design: Prospective case- control study

Setting: Department of Gynecology and Obstetrics of the Medical University of Vienna in co- operation with the Core Facilities Proteomics of the Medical University of Vienna

Population: Twenty female patients with SUI and twenty healthy patients who attend the outpatient clinic of the Department of Obstetrics and Gynaecology, Medical University of Vienna (sample size calculation FDR 0.05, power of 80%, assumed proportion of true H0 0.95, assumed standardized effect size of 1)

Methods: Examinations to be carried out: patient history, provocative stress test, ICIQ short form questionnaire, residual urine volume (ultrasound) and urine analysis (dipstick testing). A urine sample is obtained from the patient after spontaneous micturition, to which protease inhibitor will be added immediately. Two serum blood vials (each 9ml) are taken from a peripheral vein of the patient for routine laboratory and further research.

Proteomics analysis will be performed using chromatographic separation (LC) with mass spectrometric detection (MS).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Methods:

Sample preparation and analysis will include:

  1. Sample collection and immediate addition of protease inhibitor cocktail (Roche, Complete Protease Inhibitor Cocktail).
  2. Urine centrifugation and filtration for removal of cell debris.
  3. Protein precipitation by applying methanol/chloroform separation for removal of all possible non-proteinic substances.
  4. Protein digestion applying in-solution trypsin, pepsin, and Glu-C.

  5. Peptide separation using nano HPLC and different chromatographic approaches.

    1. Reversed phase (RP) separation of peptides and MS detection
    2. Separation of peptides using HILIC (hydrophilic Interaction Liquid Chromatography) for discrimination of polar peptides.
    3. In addition to RP and HILIC directly coupled to MS, digested peptides will be separated using multidimensional approaches. Weak anion exchange columns operated under HILIC conditions will be used to separate peptides carrying posttranslational modifications such as phosphorylation or acetylation, thus, increasing the dynamic range of detection. During this separation, fractions will be collected and re-injected onto the RP and HILIC with MS detection.
    4. All nano HPLC separations will be performed using biocompatible separation system.

Mass spectrometric analysis of digested peptides will be performed using two different detection methods: ion-trap and the time-of-flight (qToF) MS. qToF mass spectrometric detection and analysis will also be used for the label-free quantitation of peptides and proteins detected in samples. All measurements will be performed in triplicate to provide corrections for technical variability of separation and ionization.

General database search will be performed using the Human SwissProt Database in its actual version at the time of analysis. Data search will be performed using Mascot (http://www.matrixscience.com/) and X!Tandem (http://www.thegpm.org/tandem/) search machines, and the final data allocation and filtering by using Scaffold (www.proteomsoftware.com).

Statistical analysis:

Data analysis will be conducted with the bioconductor package limma. Before data analysis, data will be filtered by excluding proteins with measurements with a low interquartile range. Groups will be compared by moderated paired t-statistics adjusting for age. Adjustment for multiple testing will be done by Benjamini-Hochberg correction controlling the FDR at 0.05.

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medical University of Vienna, Department of Obstetrics and Gynaecology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited from the urogynaecology and general gynecology outpatient clinic of the Department of Obstetrics and Gynaecology at the Medical University of Vienna

Description

Inclusion Criteria:

  • patients with stress urinary incontinence: a history of symptoms of stress urinary incontinence for at least 3 months (including anamnestic complaints of involuntary leakage on effort or exertion or on sneezing or coughing) and a positive provocative stress test (defined as an observed transurethral loss of urine that was simultaneous with a cough or Valsalva maneuver at a bladder volume of 300ml or less)
  • patients capable of independent toiling
  • patients who are able to fully understand all study procedures and to provide written informed consent to study participation
  • age ≥ 18
  • patients after vaginal delivery

Exclusion Criteria:

  • patients who have previously been treated for SUI (both surgical or pharmacological treatment)
  • patients who have a medical history of uncontrolled overactive bladder (OAB) or urinary incontinence other than SUI (including anamnestic complaints on involuntary urine leakage accompanied by or immediately preceded by urgency, not stress induced)
  • patients with well established neurological disorder (e.g. Multiple Sclerosis, Parkinson's disease, Alzheimer's disease)
  • patients with pelvic organ prolapse stage ≥ II (ICS classification)
  • patients with a clinically significant bladder outlet obstruction and/or patients with a post void residual volume (PVR) > 100ml
  • patients with a history of acute urinary retention or history of repeated catheterizations due to acute urinary retention within the last 3 months prior to the day of informed consent
  • patients with an indwelling catheter and patients practicing intermittent self- catheterization
  • patients who have undergone a bladder biopsy or any other minor pelvic surgical intervention less than 30 days prior to the day of informed consent
  • patients with a history of bladder cancer
  • patients with acute or recurrent urinary tract infection and/or unexplained haematuria
  • patients with stone(s) in the bladder or urethra and upper tract stone disease causing symptoms
  • patients with evidence of renal insufficiency (creatinine > 1.5x upper limit of normal)
  • patients with evidence of hepatic disease (total bilirubin >1.5x upper limit of normal, or AST or ALT or alkaline phosphatase >2x upper limit of normal)
  • patients with a history of alcohol and/or other drug abuse
  • patients who are unable and/or unlikely to comprehend and follow the study procedures and instructions
  • patients who are pregnant or lactating
  • patients with serious medical conditions who, in the opinion of the investigators, should not participate in this study

The control group is represented by patients with the same inclusion and exclusion criteria as the case group, except stress urinary incontinence.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
stress urinary incontinence
Patients presenting with stress urinary incontinence according to the inclusion and exclusion criteria
Other: collection of urine and blood sample
healthy controls
healthy women with the same inclusion and exclusion criteria as the case group, except for stress urinary incontinence
Other: collection of urine and blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mass spectrometric measuring of urinary proteomic secretome in diseased and healthy subjects (sequence coverage and number of identified proteins)
Time Frame: The primary outcome measure will be assessed for each participant in a time frame of 4-7 days after recruitment
Comparison of protein concentrations based on number of identified proteins and mass spectrometric spectral count for patients with stress urinary incontinence and healthy controls.
The primary outcome measure will be assessed for each participant in a time frame of 4-7 days after recruitment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Heinz Kölbl, Univ.-Prof.Dr.Dr.h.c., Medical University of Vienna, Department of Obstetrics and Gynaecology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

November 18, 2013

First Submitted That Met QC Criteria

December 23, 2013

First Posted (Estimated)

December 30, 2013

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EK 1788/2013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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