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CompletedNCT04049019Updated Jul 7, 2023

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

An interventional study of Urine collection through a collecting device (Uridome®) for maximum 1 week and Urine collection in Nocturnal Enuresis, sponsored by University of Aarhus. Completed at 1 site in Denmark. Open to male participants aged 6 Years to 14 Years. Per ClinicalTrials.gov, last updated 2023-07-07.

Sponsored by University of Aarhus · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
6 Years to 14 Years
Sex
Male
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

03

Who can participate

Ages eligible
6 Years to 14 Years
Sexes eligible
Male
Accepts healthy volunteers
No

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

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.

04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    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.

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

  • Active comparator
    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.

    Diagnostic Test: Urine collection

Interventions

  • Diagnostic testUrine 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.

  • Diagnostic testUrine collection

    The child will collect: * Urine at bedtime. * First morning voided volume

05

What researchers measure

Primary outcomes

  1. Proteins.

    By using mass spectrometry (proteomics). For all children, any proteins related to nocturnal polyuria will be detected.

    Time frame: Up to 1 week.

  2. Metabolites.

    By targeted mass spectrometry.

    Time frame: Up to 1 week.

Secondary outcomes

  1. Total urine volume in each sample.

    A urine volume for the "dry night" (first morning voided volume) and "wet night" (nighttime urine production + first morning voided volume) will be calculated.

    Time frame: Up to 1 week.

  2. Concentration of creatinine in the urine samples.

    A level for the "dry night" and "wet night" will be calculated.

    Time frame: Up to 1 week.

  3. Osmolality in the urine samples.

    By freezing-point depression. A level for the "dry night" and "wet night" will be calculated.

    Time frame: Up to 1 week.

06

Study locations

1 site
  • Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital
    Aarhus, Jylland 8200, Denmark
07

References and documents

Publications

  • 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. PubMed 21511300 ↗
  • 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. PubMed 18432533 ↗
  • 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. PubMed 14764133 ↗
  • 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. PubMed 9634030 ↗
  • 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. PubMed 9599731 ↗
  • 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. PubMed 20006865 ↗
  • 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. PubMed 10458430 ↗
  • 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. PubMed 10209568 ↗
  • 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. PubMed 2705537 ↗
  • 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. PubMed 11196246 ↗
  • 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. PubMed 18206924 ↗
  • 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. PubMed 20579671 ↗
  • 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. PubMed 22927352 ↗
  • 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. PubMed 17727573 ↗
  • 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. PubMed 25333063 ↗

Individual participant data

Plan to share: Yes

08

Registry details

Key details

Study ID
NCT04049019
Lead sponsor
University of Aarhus
Responsible party
Sponsor
First posted
Aug 7, 2019
Start date
Aug 1, 2019
Primary completion
Sep 1, 2022
Completion
Sep 1, 2022
Last update
Jul 7, 2023

Study contacts

Søren Rittig, MD
principal investigator · Aarhus University Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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