Ignite Creation Date:
2024-05-06 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 2:29 PM
Study NCT ID:
NCT05318365
Status:
RECRUITING
Last Update Posted:
2024-05-08
First Post:
2022-03-30
Brief Title:
Bladder and Bowel Dysfunction in Children
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
Bladder and Bowel Dysfunction in Children
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
Recruiting
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 investigators 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 n100 between 5-14 years and 9 months old They are randomized to 1 Medical treatment of bowel symptoms n50 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
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 investigators 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 n100 between 5-14 years and 9 months old They are randomized to 1 Medical treatment of bowel symptoms n50 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
Detailed Description:
Background Bladder and bowel dysfunction BBD is characterised by lower urinary tract symptoms LUTS accompanied by bowel complaints primarily functional constipation andor faecal incontinence To standardise the terminology used for BBD LUTS symptoms related to the disease have been defined by International Childrens 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 UTIs 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 UTIs 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 UTIs in adults However the composition of the urine microbiome in children is only sparsely investigated and its role in BBD and childhood UTIs is to the investigators 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
12 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 n100 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 n50
2 Medical treatment of bowel symptoms in accordance with the ESPGHAN guidelines combined with standard urotherapy n50
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 UTIs 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 childrens 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 eg 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 n100 was calculated for each group to achieve a power of 80 for detecting a difference in proportions of 030 between the two groups test - reference group at a two sided p-value of 005
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 UTIs compared to BBD children without recurrent UTIs
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 Faiths phylogenetic diversity Shannon diversity index and Pielous 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 Students t-test or one-way ANOVA and Tukeys 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 005 p001 and p0001
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
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 UTIs 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 UTIs 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 UTIs in adults However the composition of the urine microbiome in children is only sparsely investigated and its role in BBD and childhood UTIs is to the investigators 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
12 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 n100 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 n50
2 Medical treatment of bowel symptoms in accordance with the ESPGHAN guidelines combined with standard urotherapy n50
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 UTIs 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 childrens 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 eg 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 n100 was calculated for each group to achieve a power of 80 for detecting a difference in proportions of 030 between the two groups test - reference group at a two sided p-value of 005
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 UTIs compared to BBD children without recurrent UTIs
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 Faiths phylogenetic diversity Shannon diversity index and Pielous 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 Students t-test or one-way ANOVA and Tukeys 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 005 p001 and p0001
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None