Sleep Architecture in Valproate-induced Nocturnal Enuresis in Primary School and Preschool Children.

Epilepsy Clinical Trial

Official title:

PSG in Valproate-induced Nocturnal Enuresis in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04191863
• Other study ID #: Mansoura University Hospital 8
• Status: Completed
• Start date: September 1, 2018
• Est. completion date: August 1, 2019

Study information

• Verified date: May 2020
• Source: Mansoura University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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."

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: August 1, 2019
• Est. primary completion date: June 1, 2019
• Gender: All
• Age group: 5 Years to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Enuresis
• Epilepsy
• Nocturnal Enuresis
• Urinary Incontinence

Intervention

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

Locations

Country	Name	City	State
Egypt	Mansoura University Hospital	Mansoura

Sponsors (1)

Lead Sponsor	Collaborator
Mansoura University Hospital

Country where clinical trial is conducted

Egypt, 

References & Publications (11)

Alshahrani A, Selim M, Abbas M. Prevalence of nocturnal enuresis among children in Primary Health Care Centers of Family and Community Medicine, PSMMC, Riyadh City, KSA. J Family Med Prim Care. 2018 Sep-Oct;7(5):937-941. doi: 10.4103/jfmpc.jfmpc_32_18. — View Citation

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.

Cattaneo CI, Ressico F, Valsesia R, D'Innella P, Ballabio M, Fornaro M. Sudden valproate-induced hyperammonemia managed with L-carnitine in a medically healthy bipolar patient: Essential review of the literature and case report. Medicine (Baltimore). 2017 Sep;96(39):e8117. doi: 10.1097/MD.0000000000008117. Review. — View Citation

Clayton-Smith J, Bromley R, Dean J, Journel H, Odent S, Wood A, Williams J, Cuthbert V, Hackett L, Aslam N, Malm H, James G, Westbom L, Day R, Ladusans E, Jackson A, Bruce I, Walker R, Sidhu S, Dyer C, Ashworth J, Hindley D, Diaz GA, Rawson M, Turnpenny P. Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability. Orphanet J Rare Dis. 2019 Jul 19;14(1):180. doi: 10.1186/s13023-019-1064-y. — View Citation

Fritz G, Rockney R, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J, Rue D, Shaw JA, Stock S, Kroeger Ptakowski K; Work Group on Quality Issues; AACAP. Practice parameter for the assessment and treatment of children and adolescents with enuresis. J Am Acad Child Adolesc Psychiatry. 2004 Dec;43(12):1540-50. Review. — View Citation

Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A, Lowenstein D, Pellock J, Riviello J, Sloan E, Treiman DM. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61. doi: 10.5698/1535-7597-16.1.48. — View Citation

Hamed A, Yousf F, Hussein MM. Prevalence of nocturnal enuresis and related risk factors in school-age children in Egypt: an epidemiological study. World J Urol. 2017 Mar;35(3):459-465. doi: 10.1007/s00345-016-1879-2. Epub 2016 Jun 15. — View Citation

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.

Romoli M, Mazzocchetti P, D'Alonzo R, Siliquini S, Rinaldi VE, Verrotti A, Calabresi P, Costa C. Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences. Curr Neuropharmacol. 2019;17(10):926-946. doi: 10.2174/1570159X17666181227165722. Review. — View Citation

Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol. 2016 Feb;15(2):210-218. doi: 10.1016/S1474-4422(15)00314-2. Epub 2015 Dec 5. Review. — View Citation

Yamak WR, Hmaimess G, Makke Y, Sabbagh S, Arabi M, Beydoun A, Nasreddine W. Valproate-induced enuresis: a prospective study. Dev Med Child Neurol. 2015 Aug;57(8):737-41. doi: 10.1111/dmcn.12737. Epub 2015 Mar 25. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nocturnal enuresis	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	6 months
Secondary	Side effects of valproic acid	The incidence of the side effects that happened in children during treatment by valproate.	6 month