Bladder and Bowel Dysfunction in Children

November 1, 2022 updated by: University of Aarhus

Background:

Bladder and bowel dysfunction (BBD) is characterized by lower urinary tract symptoms accompanied by bowel complaints. BBD is a common condition in childhood. The present treatment strategy for BBD is a step-wise approach starting with management of bowel symptoms before initiation of standard urotherapy and further medical treatment of LUTS symptoms. This is, however, based on clinical experience and few retrospective, non-randomized studies and high-level evidence of the succession of the elements in treatment of BBD children is missing.

Our microbiome, and its role in health and disease, has gained increased focus during the past years. Studies suggest the urine and gut microbiome to be critical for maintenance of a well-functioning bladder- and bowel system. The microbiome in children is only sparsely investigated and its role in BBD is to the investigator's knowledge still unexplored.

Study 1:

Aim: To investigate if combination therapy is more effective in treating urinary incontinence in BBD children.

Materials and methods: A prospective randomized multicentre study on children with BBD (n=100) between 5-14 years and 9 months old. They are randomized to: 1) Medical treatment of bowel symptoms (n=50) or 2) Medical treatment of bowel symptoms combined with standard urotherapy.

The effect of treatment will be evaluated after 3 months. Primary endpoint: Resolution of incontinence after treatment. Secondary endpoint: Improved quality of life after successful treatment of urinary incontinence.

Study 2:

Aim: To investigate the urofecal microbiome in children with BBD

Materials and methods:

  1. A cohort study to investigate, whether the urofecal microbiome can predict response to treatment and whether it changes during treatment period
  2. A case control study to investigate whether the urofecal microbiome is different in children with BBD and recurrent UTI 's and children with BBD without recurrent UTI 's.

The study population consists of children with BBD included in study 1. A urine-, stool sample and a perineum swab will be collected from all participants before and after treatment. Bacterial DNA will be extracted and the microbiome will be determined.

Perspectives:

BBD is a common condition in childhood. It is associated with a considerable psychological burden and a risk of more severe physical complications.

The studies will provide basic knowledge about characteristics of the BBD patients and contribute new information about the optimal treatment of BBD children.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background Bladder and bowel dysfunction (BBD) is characterised by lower urinary tract symptoms (LUTS) accompanied by bowel complaints, primarily functional constipation and/or faecal incontinence. To standardise the terminology used for BBD, LUTS symptoms related to the disease have been defined by International Children's Continence Society (ICCS).

The prevalence of BBD is probably underestimated but studies suggest BBD to be present in up to 20 % of school children and to represent up to 40% of paediatric urology consults.

Embryological, anatomical and functional interactions between the rectum and urinary bladder are well known. Bladder and bowel are anatomically closely related and share innervation from the parasympathetic S2-S4 and sympathetic L1-L3 nerve roots.

Research on successful treatment of BBD is sparse, with only few retrospective, non-randomized studies, documenting that treatment of defecation problems in children with BBD enhances successful management of lower urinary tract disturbances such as daytime urinary incontinence (DUI), enuresis and urinary tract infections (UTI's). Based on this knowledge and clinical experience, the present treatment strategy for children with BBD is a step-wise approach starting with management of bowel symptoms before initiation of standard urotherapy and further medical treatment of LUTS symptoms. Standard urotherapy encompasses information and demystification of the disorder along with behavioural modification such as timed voiding, proper voiding posture, avoidance of holding manoeuvers and balanced fluid intake. Standard urotherapy is well-established as first-line treatment for children with LUTS. However, high-level evidence of the succession of the elements in treatment of BBD children is missing.

BBD is commonly associated with vesicoureteral reflux (VUR) and recurrent UTI's, which may lead to renal scarring , kidney failure and hypertension. It is a potential cause of significant physical and psychosocial burden for children and families. Therefore, optimization of treatment is critical to avoid secondary comorbidities.

Our microbiome, and its role in health and disease, has gained increased focus during the past few years.

Studies suggest the urine and gut microbiome to be critical for maintenance of a well-functioning bladder- and bowel system.

Dysbiosis is defined by the presence of unbalanced and disease-promoting composition of the microbiome. It is well-established that dysbiosis is associated with constipation in children and the condition is suspected to be involved in urological disorders such as overactive bladder, urge, incontinence and recurrent UTI's in adults. However, the composition of the urine microbiome in children is only sparsely investigated and its role in BBD and childhood UTI's is to the investigator's knowledge still unexplored.

Study 1: Does successful treatment of bowel symptoms resolve urinary incontinence in children with BBD? Aim and hypothesis Aim: To investigate if effective treatment of bowel problems resolves urinary incontinence in BBD children.

The hypothesis of the investigators is:

  1. Treatment of bowel symptoms resolves urinary incontinence in BBD children.
  2. It is more effective to initiate urotherapy from the beginning in combination with treatment of bowel symptoms instead of the present regime where bowel symptoms are managed before urotherapy is started.
  3. Succesful treatment of urinary incontinence in children with BBD improves their quality of life.

1.2 Materials and methods A prospective multicentre randomised study on children with BBD referred to the Pediatric Incontinence and Gastroenterology outpatient clinics at the Department of Pediatrics, Aarhus University Hospital, Aalborg University Hospital and Regional Hospital Goedstrup.

Children (n=100) between 5-14 years and 9 months diagnosed with BBD at their first visit to the outpatient clinic will be included if they meet in- and exclusion criteria.

The included children will be randomised to one of the following treatments:

  1. Medical treatment of bowel symptoms in accordance with the guidelines of The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=50)
  2. Medical treatment of bowel symptoms in accordance with the ESPGHAN guidelines combined with standard urotherapy (n=50)

At first visit to the outpatient clinic, enrolled children will undergo physical examination including neurological examination. Data on medical history will be collected including number of and time for UTI's. Participants will be asked to fill in a 48-hour flow-volume chart and in case of enuresis nocturna the chart will also include registration for 7 nights. Participants will also fill in "Toerfisk" which is a validated tool to monitor severity of urinary incontinence. Routine uroflowmetry will be performed for further evaluation of lower urinary symptoms. A urine sample will be collected for diagnosing on-going UTI and for microbiome analysis in study 3. The children will be screened for constipation in accordance with the ROME IV criteria. Rectal examination will be performed or transrectal diameter will be evaluated with point-of-care ultrasound. Stool sample and perineum swab will be collected for microbiome analysis.

The psychological burden from the children´s BBD condition will be evaluated by PinQ, a validated questionnaire used for assessment of quality of life according to the incontinence issue of the patients.

All participants will be informed about bladder and bowel function in order to demystify the disorder. Daily defecation will be induced by reconditioning to normal bowel habits through timed toilet sitting and daily administration of laxatives (e.g. PEG3350) in relevant dosage according to the ESPGHAN guidelines.

Participants randomized to combined medical treatment for bowel symptoms and urotherapy will be instructed in urotherapy in accordance with earlier description.

After 1 month of treatment the participants will be contacted by telephone to ensure compliance and for adjustment of laxative dose depending on the bowel symptoms.

The second visit in the outpatient clinic will be after 3 months of treatment. Before the consultation, the participants will be asked to fill in a second flow-volume chart as well as "Toerfisk" and PinQ questionnaires. Uroflowmetry will be repeated and a second urine sample will be collected for stix, culturing and microbiome analysis. Bowel symptoms will be evaluated using ROME IV, rectal examination and transrectal diameter and a second stool sample and perineum swab will be collected for microbiome analysis for study 3.

Data storage Data will be entered into RedCap, which is a secure web platform for building and managing online databases.

Power estimation The sample size (n=100) was calculated for each group to achieve a power of 80% for detecting a difference in proportions of 0.30 between the two groups (test - reference group) at a two sided p-value of 0.05.

Study 2: Urine, perineal and gut microbiome in children with BBD before and after treatment Aim and hypothesis To investigate the urine, perineal and gut microbiome in children with BBD before and after treatment.

The hypothesis of the investigators is that

  1. Response to treatment can be predicted by the composition of the urine, perineal and gut microbiome in children with BBD.
  2. The composition of the urine, perineal and gut microbiome is different in BBD children with recurrent UTI's compared to BBD children without recurrent UTI's.
  3. The urine, perineal and gut microbiome in children with BBD will change when bladder and bowel symptoms successfully treated.

Materials and methods

The study is a multicentre study consisting of two elements:

  1. a cohort study to investigate, whether the urine, perineal and gut microbiome can predict response to treatment and whether it changes during treatment period
  2. a case control study to investigate whether the urine, perineal and gut microbiome is different in children with BBD and recurrent UTI 's and children with BBD without recurrent UTI 's.

The study population consists of children with BBD included in study 1.

Collection and analysis of samples A urine-, stool sample and a perineum swab will be collected from all participants before initiation of treatment and after 3 months of treatment as described in study 1. Bacterial DNA will be extracted and the microbiome will be determined.

Data storage Biological material will be pseudonymised and stored in a -80 degree fridge until analysis is performed.

Statistical analysis for all 3 studies Distribution and variance will be analysed by QQ plot, Shapiro-Wilks test and Bartletts test. Microbiota alpha-diversity will be addressed by ASV richness, Faith's phylogenetic diversity, Shannon diversity index, and Pielou's evenness index. Beta-diversity analysis will include principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity, weighted and unweighted UniFrac. Parametric data will be compared using Student's t-test or one-way ANOVA and Tukey´s post hoc test, while non-parametric data will be compared with Kruskal-Wallis test or Mann-Whitney U-test. Chi Squared test will be used for proportions. Level of significance will be as following *: p <0.05, **: p<0.01 and ***: p<0.001.

Ethics The studies will be conducted in accordance with the Declaration of Helsinki. All side effects will be handled in accordance with the actual legislation. No risk or unknown side effects are expected to urotherapy or medical treatment of bowel symptoms. No risk, side effects or discomfort is expected from collection of urine, stool and perineum samples or from uroflowmetry or transabdominal ultrasound.

Perspectives BBD is a common condition in childhood. It is associated with a considerable psychological burden and a risk of more severe physical complications.

The term BBD is recently defined and therefore only sparsely investigated. The studies will provide basic knowledge about characteristics of the BBD patients and contribute new information about the optimal treatment of BBD children.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

  • Name: Sofie Axelgaard, MD
  • Phone Number: +45 61460024
  • Email: sofiaxel@rm.dk

Study Contact Backup

Study Locations

  • Denmark
      • Aalborg, Denmark, 9000
        • Not yet recruiting
        • Aalborg University Hospital
        • Contact:
          • Søren Hagstrøm, M.D., professor
          • Email: soha@rn.dk
      • Aarhus, Denmark, 8000
      • Herning, Denmark, 7400
        • Recruiting
        • Goedstrup Regional Hospital
        • Contact:
          • Sofie Axelgaard, M.D.
          • Phone Number: +45 61460024
          • Email: sofiaxel@rm.dk
        • Contact:

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

3 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 5-14 years and 9 months at time of inclusion
  • Diagnosed with urinary incontinence and/or enuresis nocturna defined by the ICCS criteria
  • Diagnosed with constipation and/or faecal incontinence defined by the ROME IV criteria
  • Normal clinical examination
  • Parents/guardian can understand the written and spoken information
  • Informed assent to participation from both parents/guardian

Exclusion Criteria:

  • Neuropathic or anatomical abnormalities in the urinary tract or gastrointestinal canal
  • Earlier surgical intervention of the urinary tract (except circumcision)
  • Neurological illness or earlier cerebral surgical intervention
  • On-going urinary tract infection
  • On-going treatment with anticholinergics and/or β3-adenoceptoragonist
  • On-going treatment with laxatives in correct dosage (PEG3350 1-2 g/kg/day)
  • Inflammatory bowel disease
  • Other disorder affection bladder or bowel function
  • For Study 2 (microbiome): Systemic antibiotics within the past 3 months

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment of constipation and/or faecal incontinence
Medical treatment of bowel symptoms in accordance with the guidelines of The European Society for Paediatric Gastroenterology, Hepatology and Nutrition
Drug: Polyethylene Glycol 3350
PEG3350, klysma, laxoberal and magnesia will be administered in accordance with actual guidelines for treatment of constipation in children
Other Names:
  • Magnesia
  • Laxoberal
  • Glyoktylklysma
Active Comparator: Treatment of constipation and/or faecal incontinence combined with urotherapy
Medical treatment of bowel symptoms in accordance with the guidelines of The European Society for Paediatric Gastroenterology, Hepatology and Nutrition combined with standard urotherapy in accordance with International Children's Continence Society (ICCS)
Drug: Polyethylene Glycol 3350
PEG3350, klysma, laxoberal and magnesia will be administered in accordance with actual guidelines for treatment of constipation in children
Other Names:
  • Magnesia
  • Laxoberal
  • Glyoktylklysma
Behavioral: Urotherapy
Information and demystification of the disorder along with behavioural modification such as timed voiding, proper voiding posture, avoidance of holding manoeuvers and balanced fluid intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with reduction in weekly episodes of urinary incontinence
Time Frame: Evaluation after 3 months of treatment
No-response: <50% reduction, Partial response: 50 to 99% reduction, Complete response: 100% reduction.
Evaluation after 3 months of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with a change in quality of life after succesful treatment of urinary incontinence
Time Frame: Evaluation after 3 months of treatment
Tool: PinQ Questionnaire
Evaluation after 3 months of treatment

Collaborators and Investigators

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

Sponsor

University of Aarhus

Investigators

  • Study Chair: Sofie Axelgaard, MD, Department of Childhood and Adolescent Medicine, Regional Hospital Goedstrup
  • Principal Investigator: Soeren Hagstroem, Professor, MD, Department of Childhood and Adolescent Medicine, Aalborg University Hospital
  • Study Director: Luise Borch, MD, PhD, Department of Childhood and Adolescent Medicine, Regional Hospital Goedstrup
  • Study Director: Konstantinos Kamperis, MD, PhD, Department of Childhood and Adolescent Medicine, Aarhus University Hospital

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 (Actual)

September 1, 2022

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

March 30, 2022

First Submitted That Met QC Criteria

April 7, 2022

First Posted (Actual)

April 8, 2022

Study Record Updates

Last Update Posted (Actual)

November 2, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBD_Children

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on Bladder and Bowel Dysfunction

Clinical Trials on Polyethylene Glycol 3350

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe