The Effect of Indomethacin in Monosymptomatic Enuresis Nocturnal
Condition: Enuresis
MeSH terms: Enuresis; Urinary Incontinence; Nocturnal Enuresis
Study type: Interventional
Phase: Phase 4

Summary: 
      Monosymptomatic nocturnal enuresis, defined as the involuntary loss of urine during the night
      at an age where voluntary bladder control should have been attained and on the background of
      normal urinary tract function, is a rather common disease of childhood with an estimated
      prevalence of 5-10% at tha age of 7 and a spontaneous remission rate of 15% per year.

      The present study consists of two phases; an in-patient phase and an ambulatory phase.

      In the in-patient phase we will examine the regulation of sodium and the circadian rhythm of
      the hormones that affect this regulation in children with enuresis nocturnal and healthy
      children, as well as the impact of indomethacin on renal water and electrolyte excretion.

      In the ambulatory phase we will examine the efficacy and safety of a treatment modality
      consisting of a combination of dDAVP and indomethacin in patients with severe enuresis where
      dDAVP as monotherapy is inadequate.

      A significant number of children with enuresis and nocturnal polyuria do not respond to
      treatment with dDAVP. If a combination treatment with dDAVP and indomethacin proves superior
      to dDAVP alone the regimen could readily be used in those difficult to cure cases of
      enuresis.
    

Detailed description: 
      The "in-patient" phase is a comparative circadian study of three groups of participants and a
      non-placebo controlled study of the renal effects of indomethacin with special reference the
      renal handling of sodium.

      The ambulatory phase is designed as a randomized double blind, crossover placebo controlled
      for indomethacin study of the efficacy and safety of a combination treatment with
      indomethacin and dDAVP.

      In-patient phase: Primary effect parameters will be the diuresis, urinary osmolality, sodium
      excretion prior to and after the administration of indomethacin.

      Secondary effect parameters will be the following: GFR, K+ excretion, creatinine excretion,
      urea excretion, as well as urinary concentrations of aquaporin 2 (AQP2), PGE2, AVP, URO,
      Na-transporter protein, concentration of renin, ANG II, ALDO, ANP, in plasma, prior to and
      after the administration of indomethacin.

      Ambulatory phase: Primary effect parameter will be the number of dry nights achieved in the
      two treatment periods. Secondary effect parameters will be the nocturnal urine production,
      and the enuresis volumes In-patient phase: Day-night ratios will be calculated for all
      parameters tested. The circadian rhythm of hormones blood pressure and electrolyte excretion
      will be analyzed using COSINOR analysis.

      The effect of indomethacin on the parameters tested will be compared to the basal
      measurements using student's t-test, ANOVA for repeated measurements or non-parametric tests.
      All statistical inference will take place on a "protocol population" basis.

      Ambulatory phase: The efficacy of the combination treatment will be tested against placebo
      (only for indomethacin) with help of student's t-test, x2 test or non-parametric tests.

      The results from the home recordings will be compared for the two treatment periods using
      non-parametric tests. The effect parameters that will undergo statistical analysis are the
      number of wet nights, the enuresis volume and the nocturnal urine production. The analysis
      will be on the basis of intention to treat population.
    

Intervention name(s): Indomethacin
Intervention type(s): Drug
Intervention description(s): Indomethacin capsules 50 mg
Other intervention name(s): Confortid
Intervention MeSH terms: Indomethacin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Enuresis; Nocturnal; Monosymptomatic; DDAVP; Indomethacin; Randomized