Randomized, Double-Blinded, Placebo-Controlled Trial of Laxatives for Children With Urge Syndrome
Condition: Constipation
MeSH terms: Constipation
Study type: Interventional
Phase: Early Phase 1

Summary: 
      HYPOTHESIS:

      Is MiraLAX an effective treatment of pediatric urinary urge syndrome?

      OBJECTIVE:

      Polyethylene glycol (PEG) is common first-line therapy for urinary symptoms despite minimal
      evidence-based support. We performed a randomized, double-blind, placebo-controlled study of
      PEG for initial treatment of urinary urge symptoms.

      SUMMARY:

      Only patients of investigators and sub-investigators will be recruited for this study.
      Children with urinary incontinence, urinary frequency, diurnal incontinence, Urinary Tract
      Infection (UTI) and/or reflux validated by bladder/bowel symptom questionnaire to have Urge
      Syndrome (US) are eligible for this study. A standardized questionnaire of bowel/bladder
      activity will be administered and a KUB obtained as standard of care at entry to the study. A
      standard 1-day voiding diary will be completed at home before beginning therapy. To exclude
      patients potentially still in the process of toilet training, only subjects 4 years of age
      and older will be studied. Other exclusion criteria will include known neurological
      disorders, a diagnosis of attention deficit disorder, bladder symptoms less than 6 months in
      duration at presentation, other bladder dysfunctions besides US, a history of anorectal
      malformation and pregnancy. Based upon prior experience that patients with encopresis were
      not likely to achieve improved stooling with only a few weeks of laxative therapy, they will
      also be excluded.

      Those accepted into the study will be randomized to receive either laxative or placebo once
      daily for one month. Preparation of the laxative and placebo and patient randomization will
      be performed by the Children's Medical Center Investigational Drug Pharmacist. Premixed study
      medications will be available at the Urology clinic ready to be dispensed to the patient by
      the study coordinator after being screened and randomized. Dosage includes children age 4-6
      years (8.5 gms) and children 7-10 years (17gms). The medication will be divided into daily
      doses by the Investigational Pharmacist. Written and verbal instructions, both in English and
      Spanish, will be provided to the parents/guardian of the subjects.

      The Investigational Drug Pharmacist will be blinded to all patient data, and physicians and
      nurses evaluating patients will be blinded to randomization of these patients to laxative
      versus placebo arms.
    

Detailed description: 
      Urge Syndrome (US) is the most common non-neurogenic voiding dysfunction in children beyond
      the usual age for toilet training, and is characterized by urinary frequency and urgency,
      holding maneuvers, and diurnal incontinence. Urodynamics testing has determined these
      symptoms result from uninhibited bladder contractions, and so anticholinergic drugs that
      control these contractions are the mainstay of therapy typically given in six monthintervals
      until the condition resolves. Beyond the embarrassment that may accompany urinary
      incontinence, US has been linked to urinary tract infection (UTI) and vesicoureteral reflux.
      Specifically, among females with UTI, at least 40% also have US, and US has been identified
      as a cause for reflux and a factor that delays its otherwise expected spontaneous resolution.
      Consequently, identification and treatment of US are important to the management of children
      with UTI, reflux and/or incontinence.

      Constipation also has been associated with UTI, vesicoureteral reflux, and urinary
      incontinence in children. Although these observations date at least to the 1950s, relatively
      few studies have attempted either to establish the incidence of constipation found with these
      various pediatric urologic conditions, or to document the impact of bowel therapy upon their
      management. Of these, Yazbeck et al studied 47 children with recurrent UTI and noted all were
      constipated and had uninhibited bladder contractions during urodynamics testing. Therapy
      directed toward relief of constipation resolved bladder symptoms in 25%. Loening-Baucke
      reported 46% of 234 children attending a university-based encopresis clinic also experienced
      urinary incontinence, which diminished with laxative therapy. A recent evaluation of 582
      children with US estimated that 16% were also constipated based upon a history of bowel
      activity.

      We have been concerned about the apparent association between US and constipation, especially
      since anticholinergic drugs commonly prescribed for uninhibited bladder contractions could
      exacerbate underlying stool retention and thereby prolong bladder dysfunction. It is also our
      experience that parents are not very familiar with bowel activity of their children after the
      usual age of toilet training, making history potentially unreliable for diagnosing
      constipation. Therefore, we started recommending a brief course of laxatives for all patients
      presenting with US, reserving anticholinergics for those whose bladder symptoms persisted. In
      a retrospective review of 110 children, we found 34% had relief of bladder symptoms with
      laxatives alone, so that anticholinergic medications were not then required, and the history
      of whether the child was constipated or not did not predict response. However, this study has
      been criticized for not being placebo-controlled.

      Given the potential impact of this observation for the management of children with not only
      urinary incontinence but also UTI and reflux who have US, we now propose a prospective,
      randomized, double-blinded, placebo-controlled study of the impact of laxative therapy upon
      children with US.
    

Intervention name(s): MiraLAX; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): Every subject will be given one bottle of the polyethylene glycol/placebo, divided into daily doses and depending on the patient's age, will be instructed to take 8.5 grams or 17 grams of the medication dispensed in daily dose vials to be mixed with water or juice. They will take the medication once a day for one month.; Every subject will be given one bottle of the polyethylene glycol/placebo, divided into daily doses and depending on the patient's age, will be instructed to take 8.5 grams or 17 grams of the medication dispensed in daily dose vials to be mixed with water or juice. They will take the medication once a day for one month.
Other intervention name(s): Polyethylene glycol; Dextrose
Intervention MeSH terms: Polyethylene glycol 3350
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A prospective randomized, double-blind, placebo controlled study was performed to determine whether placebo-controlled versus Polyethylene glycol (MiraLAX) was effective for decreasing OAB symptoms.
Masking: Double (Participant, Investigator)
Primary purpose: Screening
Keywords: Bowel and bladder dysfunction; Constipation; MiraLAX; Overactive bladder; Polyethylene glycol; Urinary urgency