Biomarkers in Urine for Children With Monosymptomatic Nocturnal Enuresis and Nocturnal Polyuria

NCT ID: NCT04049019

Last Updated: 2023-07-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-01

Study Completion Date

2022-09-01

Brief Summary

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The aim of the study is to identify protein markers in relation to the enuresis related nocturnal polyuria by using mass spectrometry on nocturnal urine samples. A biomarker for nocturnal polyuria would simplify an important part of the clinical characterization of enuresis patients.

Detailed Description

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Involuntary voiding during sleep, nocturnal enuresis (NE), affects 7-10 % of all 7-year-olds, and 0.5-2 % of young adults. Night-time polyuria is one of the main pathogenic mechanisms. Today, the only method to diagnose nocturnal polyuria is home recordings involving diaper weight and registrations of first morning voids, which is very time-consuming. By using mass spectrometry (proteomics and metabolomics) on nocturnal urine samples from children with NE, the investigators aim to identify protein markers in relation to nocturnal polyuria. The perspective is to simplify an important part of the clinical characterization of NE patients.

This hypothesis-generating pilot project will be performed on 10 boys with NE. The children will have to collect:

* Urine at bedtime on a wet and a dry night.
* Urine during a wet night through a collecting device (non-invasive).
* First morning voided volume following both a wet and a dry night.

Furthermore, we will include 10 children without NE, who will collect urine during a dry night (first morning voided volume).

Endpoints are any biomarkers in urine found to be associated with nocturnal polyuria.

The proteomics and metabolomics methodologies are available at the proteomics core facility of Research Unit for Molecular Medicine, Dept. of Clinical Medicine, Aarhus University Hospital.

Based on the analytical uncertainty of the protein analysis methods, 10 samples are sufficient for detecting down to two-fold alterations in protein levels (p\<0.05). By using state of the art mass spectrometry, the difference in any protein level between 1) the total urine amount on a wet and a dry night, and 2) first morning voided volume on a wet and a dry night, will be evaluated. Furthermore, difference in urine composition between children with NE and healthy children will be evaluated. Student's t-test with significance level at p\<0.05 will be used.The amount of proteins in each urine sample will be correlated to the total amount of proteins in the respective sample.

Conditions

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Nocturnal Enuresis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

10 boys with nocturnal enuresis and 10 healthy boys will be included for urine collection.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Urine collection, children with nocturnal enuresis

The child ́s weight and height will be registered. The children's urine will be tested for infection with a dipstick urinalysis.

The child will be asked to perform home recordings for seven days consisting of measurements of diaper weight and first morning voided volume and a two-day frequency-volume chart.

Group Type EXPERIMENTAL

Urine collection through a collecting device (Uridome®) for maximum 1 week

Intervention Type DIAGNOSTIC_TEST

The child will collect:

* Urine at bedtime before a wet and a dry night.
* Urine during a wet night through a collecting device.
* First morning voided volume following both a wet and a dry night.

Urine collection, healthy children

The child ́s weight and height will be registered. The children's urine will be tested for infection with a dipstick urinalysis.

Group Type ACTIVE_COMPARATOR

Urine collection

Intervention Type DIAGNOSTIC_TEST

The child will collect:

* Urine at bedtime.
* First morning voided volume

Interventions

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Urine collection through a collecting device (Uridome®) for maximum 1 week

The child will collect:

* Urine at bedtime before a wet and a dry night.
* Urine during a wet night through a collecting device.
* First morning voided volume following both a wet and a dry night.

Intervention Type DIAGNOSTIC_TEST

Urine collection

The child will collect:

* Urine at bedtime.
* First morning voided volume

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Monosymptomatic nocturnal enuresis with at least one dry night per week.
* Nocturnal polyuria defined as nocturnal urine production on wet nights greater than 130 % of expected bladder capacity for age.
* Normal bladder capacity defined as maximum voided volume excluding first morning voided volume bigger than expected bladder capacity for age.

Exclusion Criteria

* Recurrent urinary tract infections.
* Anamnestic, clinical or laboratory findings that can be related to diseases or conditions that might affect the parameters investigated.
* Neurological and/or known clinically significant anatomical abnormalities of the urinary tract.
* Former operations in the urinary tract.
* Ongoing medication that may interfere with the parameters tested.

If the child is receiving treatment for nocturnal enuresis (desmopressin, alarm or anticholinergics), the treatment has to be paused 1 week before urine collection.

Furthermore, we will include 10 children without nocturnal enuresis and otherwise healthy.
Minimum Eligible Age

6 Years

Maximum Eligible Age

14 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Søren Rittig, MD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital

Locations

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Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital

Aarhus, Jylland, Denmark

Site Status

Countries

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Denmark

References

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von Gontard A, Heron J, Joinson C. Family history of nocturnal enuresis and urinary incontinence: results from a large epidemiological study. J Urol. 2011 Jun;185(6):2303-6. doi: 10.1016/j.juro.2011.02.040. Epub 2011 Apr 21.

Reference Type BACKGROUND
PMID: 21511300 (View on PubMed)

Butler RJ, Heron J. The prevalence of infrequent bedwetting and nocturnal enuresis in childhood. A large British cohort. Scand J Urol Nephrol. 2008;42(3):257-64. doi: 10.1080/00365590701748054.

Reference Type BACKGROUND
PMID: 18432533 (View on PubMed)

Yeung CK, Sihoe JD, Sit FK, Bower W, Sreedhar B, Lau J. Characteristics of primary nocturnal enuresis in adults: an epidemiological study. BJU Int. 2004 Feb;93(3):341-5. doi: 10.1111/j.1464-410x.2003.04612.x.

Reference Type BACKGROUND
PMID: 14764133 (View on PubMed)

Van Tijen NM, Messer AP, Namdar Z. Perceived stress of nocturnal enuresis in childhood. Br J Urol. 1998 May;81 Suppl 3:98-9. doi: 10.1046/j.1464-410x.1998.00018.x. No abstract available.

Reference Type BACKGROUND
PMID: 9634030 (View on PubMed)

Hagglof B, Andren O, Bergstrom E, Marklund L, Wendelius M. Self-esteem in children with nocturnal enuresis and urinary incontinence: improvement of self-esteem after treatment. Eur Urol. 1998;33 Suppl 3:16-9. doi: 10.1159/000052236.

Reference Type BACKGROUND
PMID: 9599731 (View on PubMed)

Neveus T, Eggert P, Evans J, Macedo A, Rittig S, Tekgul S, Vande Walle J, Yeung CK, Robson L; International Children's Continence Society. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children's Continence Society. J Urol. 2010 Feb;183(2):441-7. doi: 10.1016/j.juro.2009.10.043. Epub 2009 Dec 14.

Reference Type BACKGROUND
PMID: 20006865 (View on PubMed)

Yeung CK, Chiu HN, Sit FK. Bladder dysfunction in children with refractory monosymptomatic primary nocturnal enuresis. J Urol. 1999 Sep;162(3 Pt 2):1049-54; discussion 1054-5. doi: 10.1016/S0022-5347(01)68062-5.

Reference Type BACKGROUND
PMID: 10458430 (View on PubMed)

Hunsballe JM, Hansen TK, Rittig S, Pedersen EB, Djurhuus JC. The efficacy of DDAVP is related to the circadian rhythm of urine output in patients with persisting nocturnal enuresis. Clin Endocrinol (Oxf). 1998 Dec;49(6):793-801. doi: 10.1046/j.1365-2265.1998.00587.x.

Reference Type BACKGROUND
PMID: 10209568 (View on PubMed)

Rittig S, Knudsen UB, Norgaard JP, Pedersen EB, Djurhuus JC. Abnormal diurnal rhythm of plasma vasopressin and urinary output in patients with enuresis. Am J Physiol. 1989 Apr;256(4 Pt 2):F664-71. doi: 10.1152/ajprenal.1989.256.4.F664.

Reference Type BACKGROUND
PMID: 2705537 (View on PubMed)

Neveus T, Lackgren G, Tuvemo T, Hetta J, Hjalmas K, Stenberg A. Enuresis--background and treatment. Scand J Urol Nephrol Suppl. 2000;(206):1-44.

Reference Type BACKGROUND
PMID: 11196246 (View on PubMed)

Kamperis K, Hagstroem S, Rittig S, Djurhuus JC. Combination of the enuresis alarm and desmopressin: second line treatment for nocturnal enuresis. J Urol. 2008 Mar;179(3):1128-31. doi: 10.1016/j.juro.2007.10.088. Epub 2008 Jan 18.

Reference Type BACKGROUND
PMID: 18206924 (View on PubMed)

Dodds PR. Re: Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children's Continence Society: T. Neveus, P. Eggert, J. Evans, A. Macedo, S. Rittig, S. Tekgul, J. Vande Walle, C. K. Yeung and L. Robson J Urol 2010; 183: 441-447. J Urol. 2010 Aug;184(2):806-7; author reply 807-8. doi: 10.1016/j.juro.2010.04.006. No abstract available.

Reference Type BACKGROUND
PMID: 20579671 (View on PubMed)

Andersen RF, Palmfeldt J, Jespersen B, Gregersen N, Rittig S. Plasma and urine proteomic profiles in childhood idiopathic nephrotic syndrome. Proteomics Clin Appl. 2012 Aug;6(7-8):382-93. doi: 10.1002/prca.201100081.

Reference Type BACKGROUND
PMID: 22927352 (View on PubMed)

Rittig S, Frokiaer J. Basis and therapeutical rationale of the urinary concentrating mechanism. Int J Clin Pract Suppl. 2007 Sep;(155):2-7. doi: 10.1111/j.1742-1241.2007.01461.x.

Reference Type BACKGROUND
PMID: 17727573 (View on PubMed)

Fernandez-Guerra P, Birkler RI, Merinero B, Ugarte M, Gregersen N, Rodriguez-Pombo P, Bross P, Palmfeldt J. Selected reaction monitoring as an effective method for reliable quantification of disease-associated proteins in maple syrup urine disease. Mol Genet Genomic Med. 2014 Sep;2(5):383-92. doi: 10.1002/mgg3.88. Epub 2014 Jun 4.

Reference Type BACKGROUND
PMID: 25333063 (View on PubMed)

Other Identifiers

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Biomarkers in MNE

Identifier Type: -

Identifier Source: org_study_id

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