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Valproate-induced Nocturnal Enuresis in Children

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ClinicalTrials.gov Identifier: NCT04191863
Recruitment Status : Completed
First Posted : December 10, 2019
Last Update Posted : December 10, 2019
Sponsor:
Information provided by (Responsible Party):
Ahmed Esmael, Mansoura University Hospital

Brief Summary:

Our study, retrospectively evaluate the characteristics of and the risk factors for the occurrence of nocturnal enuresis in epileptic children kept on valproate monotherapy.

Epileptic children with the age ranged 5 up to 15 years who were started and kept up on valproate monotherapy. In this study, a child determined to have nocturnal enuresis based on the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fourth edition: "an involuntary voiding of urine during sleep, with a severity of at least twice a week, in children aged 5 years or older, in the absence of congenital or acquired defects of the nervous system."


Condition or disease Intervention/treatment
Epilepsy Nocturnal Enuresis Other: Clinical, EEG and laboratory assessment at presentation Drug: Valproate

Detailed Description:

More than 50 years ago, valproic acid has become established as an effective broad-spectrum antiepileptic drug. It is a drug of choice in children and adult with generalized or focal types of epilepsy, and in generalized convulsive status epilepticus. It is used in migraine prophylaxis, and as a modulator of chemotherapy in cancer treatment. Moreover, valproic acid may have a potential role in neuroprotection in stroke patients and head trauma.

NE is one of the side effects of VPA treatment, and it is generally underdiagnosed or overlooked by clinicians. A comprehensive review study, about the effects of valproic acid, did not mention that nocturnal enuresis as an adverse event of the valproate however; more recent study reported variable incidence of VPA‑induced NE is 2.2-24%.

The investigator's study, retrospectively evaluate the characteristics of and the risk factors for the occurrence of nocturnal enuresis in epileptic children kept on valproate monotherapy.

Method Participants The study was conducted on 260 children with epilepsy receiving valproate monotherapy aged 5-15 years who attended the outpatient clinic of neurology departments, Mansoura University Hospital, Egypt during the period Sep 2019 to Aug 2019.

Clinical, EEG and laboratory assessment at presentation

  • The patients' history, clinical, demographic, and laboratory data were acquired.
  • The following tests and imaging studies are routinely done for epilepsy patients receiving valproate treatment and developed nocturnal enuresis, blood urea nitrogen (BUN), serum creatinine (Cr), urinary pH (before and after valproate therapy beginning and at enuresis onset), serum levels and therapeutic doses of valproate.
  • Urinary tract ultrasonography (with full and void bladder).
  • CT brain and EEG.
  • Patients were therefore assessed month to month for a follow up over a time of 6 sequential months, with extra visits as required dependent on seizure recurrence or side effects.

Follow‐up at least monthly interval for 6 month for the children kept on valproate monotherapy. Evaluation of seizure control and the reported side effects associated with valproate by the parents were determined. In this way special consideration and directly asking parents about the incidence of NE and its recurrence (daily and monthly) is mandatory.

The time from the initiation of valproate monotherapy to the beginning of NE, the daily dose and the duration of treatment of valproic acid (mg/kg) at the onset of enuresis and the serum level of valproate were reported. Also, the time of cessation of NE either spontaneous or following discontinuation of valproate was determined.

Statistical analysis

A multivariate logistic regression analysis was carried out for the following independent variables: age, weight, body weight, duration of treatment and daily dose of valproate, and serum level valproate. P-value <0.05 were considered of statistically significant results.

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Study Type : Observational
Actual Enrollment : 260 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Valproate-induced Nocturnal Enuresis in Children
Actual Study Start Date : September 1, 2018
Actual Primary Completion Date : June 1, 2019
Actual Study Completion Date : August 1, 2019


Group/Cohort Intervention/treatment
Children with enuresis
28 epileptic children with induced secondary nocturnal enuresis in valproate monotherapy.
Other: Clinical, EEG and laboratory assessment at presentation
  • The patients' history, clinical, demographic, and laboratory data were acquired.
  • The following tests and imaging studies are routinely done for epilepsy patients receiving valproate treatment and developed nocturnal enuresis, blood urea nitrogen (BUN), serum creatinine (Cr), urinary pH (before and after valproate therapy beginning and at enuresis onset), serum levels and therapeutic doses of valproate.
  • Urinary tract ultrasonography (with full and void bladder).
  • CT brain and EEG.

Drug: Valproate
valproate monotherapy
Other Name: valprioc acid

Children without enuresis
232 epileptic children without induced secondary nocturnal enuresis in valproate monotherapy.
Other: Clinical, EEG and laboratory assessment at presentation
  • The patients' history, clinical, demographic, and laboratory data were acquired.
  • The following tests and imaging studies are routinely done for epilepsy patients receiving valproate treatment and developed nocturnal enuresis, blood urea nitrogen (BUN), serum creatinine (Cr), urinary pH (before and after valproate therapy beginning and at enuresis onset), serum levels and therapeutic doses of valproate.
  • Urinary tract ultrasonography (with full and void bladder).
  • CT brain and EEG.

Drug: Valproate
valproate monotherapy
Other Name: valprioc acid




Primary Outcome Measures :
  1. Nocturnal enuresis [ Time Frame: 6 months ]
    Follow‐up at least monthly interval for 6 month for the children kept on valproate monotherapy. The incidence of nocturnal enuresis and its frequency were reported


Secondary Outcome Measures :
  1. Side effects of valproic acid [ Time Frame: 6 month ]
    The incidence of the side effects that happened in children during treatment by valproate.



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Ages Eligible for Study:   5 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
The study was conducted on 260 children with epilepsy receiving valproate monotherapy aged 5-15 years who attended the outpatient clinic of neurology departments, Mansoura University Hospital, Egypt during the period Sep 2019 to Aug 2019.
Criteria

Inclusion Criteria:

  • Epileptic children kept up on valproate monotherapy and developed nocturnal enuresis.
  • Age ranged 5 up to 15 years.

Exclusion Criteria:

  • Combined therapy with other antiepileptic drugs,
  • Abnormal cerebral imaging,
  • Poor seizure control,
  • Primary nocturnal enuresis (a child didn't accomplish any times of evening dryness -over a time of 6 successive months).
  • Congenital or acquired defects of the nervous system.
  • Urinary system anomalies, or
  • Intellectual disability.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04191863


Locations
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Egypt
Mansoura University Hospital
Mansoura, Egypt
Sponsors and Collaborators
Mansoura University Hospital
Investigators
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Principal Investigator: Esmael M Ahmed, MD Assistant Prof of Neurology

Publications:
Badv R S, Abbasi A, Ashrafi M R, Shariatmadari F, Bayat O. The Effect of Sodium Valproate on Urinary Frequency and Enuresis Compared to Carbamazepine in Children with Epilepsy, Iran J Pediatr. 2018 ; 28(6):e66083. doi: 10.5812/ijp.66083.
Kanemura H, Sano F, Ohyama T, Sugita K, Aihara M. The relationship between nocturnal enuresis and sequential changes of NAG/morning urine gravity in epileptic children treated with valproate sodium. J Pediatr Epilepsy 2015;4:61‑6.

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Responsible Party: Ahmed Esmael, Assistant Prof of Neurology, Mansoura University Hospital
ClinicalTrials.gov Identifier: NCT04191863    
Other Study ID Numbers: Mansoura University Hospital 8
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ahmed Esmael, Mansoura University Hospital:
Valproic acid, enuresis, epilepsy.
Additional relevant MeSH terms:
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Epilepsy
Enuresis
Urinary Incontinence
Nocturnal Enuresis
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Urination Disorders
Urologic Diseases
Behavioral Symptoms
Elimination Disorders
Mental Disorders
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Valproic Acid
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs