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

NCT ID: NCT04191863

Last Updated: 2020-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

260 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-09-01

Study Completion Date

2019-08-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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."

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Epilepsy Nocturnal Enuresis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Children with enuresis

28 epileptic children with induced secondary nocturnal enuresis in valproate monotherapy.

Clinical, EEG and laboratory assessment at presentation

Intervention Type OTHER

* 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.

Valproate

Intervention Type DRUG

valproate monotherapy

Children without enuresis

232 epileptic children without induced secondary nocturnal enuresis in valproate monotherapy.

Clinical, EEG and laboratory assessment at presentation

Intervention Type OTHER

* 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.

Valproate

Intervention Type DRUG

valproate monotherapy

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type OTHER

Valproate

valproate monotherapy

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

valprioc acid

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

5 Years

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Mansoura University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Ahmed Esmael

Assistant Prof of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Esmael M Ahmed, MD

Role: PRINCIPAL_INVESTIGATOR

Assistant Prof of Neurology

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mansoura University Hospital

Al Mansurah, , Egypt

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Egypt

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 31324220 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26655849 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26900382 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30592252 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28953637 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 30598936 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27306687 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 25808512 (View on PubMed)

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. doi: 10.1097/01.chi.0000142196.41215.cc.

Reference Type BACKGROUND
PMID: 15564822 (View on PubMed)

Esmael A, Elsherief M, Abdelsalam M, Bendary L, Egila H. Sleep Architecture in Valproate-Induced Nocturnal Enuresis in Primary School and Preschool Children. J Child Neurol. 2020 Dec;35(14):975-982. doi: 10.1177/0883073820944051. Epub 2020 Aug 7.

Reference Type DERIVED
PMID: 32762394 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Mansoura University Hospital 8

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Efficacy of Quetiapine for Pediatric Delirium
NCT02056171 TERMINATED PHASE1/PHASE2
Exogenous Ketone Esters for Drug Resistant Epilepsy
NCT05670847 RECRUITING PHASE2/PHASE3
Extended-release Sodium Oxybate in Children
NCT06809803 RECRUITING PHASE2