Effect of Adding Lamotrigine to Sodium Valproate in Childhood Epilepsy: Clinicolabratory Study

NCT05881928 | Not Yet Recruiting Phase 4

• 1 other identifier: lamotrigine , sodium valproate
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Epilepsy is one of the most common serious chronic brain disorders of childhood. The causes of epilepsy include :acquired brain damage, altered metabolic states, inborn brain malformations, and genetic causes. At present, antiepileptic drugs (AEDs) are the first line therapy for resistant epilepsy (RE) , and the second line is surgery , and vagus nerve stimulation . Sodium valproate (SV) is a first line anti epileptic drug that can be applied to various seizure types in children . SV has anticonvulsant activity through regulation of neuronal pathways . It has a molecular structure similar to neurotransmitter γ aminobutyric acid (GABA) resulting in GABA synergism , A serious adverse effect of the valproic acid (VPA) : is its effect on liver function with resultant drug-induced hepatotoxicity, hyperammonemia . Lamotrigine (LTG) is a second generation AED . LTG belongs to the sodium channel blocking class of antiseizure medications (ASMs). Lamortigine side effects include severe rash, fever, lymphadenopathy, hepatic dysfunction, blood disorder,and disseminated intravascular coagulation and Stevens-Johnson syndrome (SJS) . the aim : Evaluation of the efficacy and safety of adding lamotrigine to sodium valproate in epileptic children not responding to SV alone for 6 months. Moreover, the investigators will evaluate the effects of this addition ,appearance of side effects,laboratory evaluation and EEG changes 50 epileptic patients receive SV for 6 months without complete remission for participants, the investigators will add lamotrigine for 6 months.

Conditions

Epilepsy; Lamotrigine; Sodium Valproate Adverse Reaction

Outcome Measures

Primary Outcomes (1)

• Weight

  Weight in kilogramme will be measured in 50 participants

  6 months

Secondary Outcomes (5)

• liver function tests

  6months

• serum ammonia.

  6months

• complete blood count

  6 months

• E.E.G

  6months

• Serum concentration of LTG

  6 months

Study Arms (1)

50 epileptic patients receive SV for 6 months , for whom add lamotrigine for 6 month

OTHER

50 epileptic patients receive SV for 6 months at dose 30 mg.kg.day, for whom add lamotrigine for 6 month at dose 0.5 mg.kg.day then add 0.5 mg.kg.day every 2 weeks

Drug: Sodium Valproate 500 Mg Prolonged-Release Oral Tablet; Drug: Lamotrigine; Device: E.E.G

Interventions

Sodium Valproate 500 Mg Prolonged-Release Oral Tablet DRUG

sodium valproate tablet30 mg / kg / day , maximum 1500mg / day . LTG :

50 epileptic patients receive SV for 6 months , for whom add lamotrigine for 6 month

Lamotrigine DRUG

lamotrigine tablet 0.5 mg/kg for 2 weeks in two divided doses , increased in 0.5mg/kg/day increments every 2weeks .

50 epileptic patients receive SV for 6 months , for whom add lamotrigine for 6 month

E.E.G DEVICE

device recording of brain activity. During this painless test, small sensors are attached to the scalp to pick up the electrical signals produced by the brain. These signals are recorded by a machine and are looked at by a doctoris

50 epileptic patients receive SV for 6 months , for whom add lamotrigine for 6 month

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male or female, ages 2 - 12years.
• epileptic children on sodium valproate for 6 months without complete remission.

You may not qualify if:

• other neurological disorders .
• Allergic to LTG.
• Liver dysfunction.
• kidney dysfunction .
• Not cooperating with this study

Sponsors & Collaborators

• Assiut University: lead

Related Publications (10)

• Altunbasak S, Baytok V, Tasouji M, Herguner O, Burgut R, Kayrin L. Asymptomatic hyperammonemia in children treated with valproic acid. J Child Neurol. 1997 Oct;12(7):461-3. doi: 10.1177/088307389701200709. No abstract available.

  PMID: 9373804 BACKGROUND

• Armeno M, Verini A, Del Pino M, Araujo MB, Mestre G, Reyes G, Caraballo RH. A Prospective Study on Changes in Nutritional Status and Growth Following Two Years of Ketogenic Diet (KD) Therapy in Children with Refractory Epilepsy. Nutrients. 2019 Jul 14;11(7):1596. doi: 10.3390/nu11071596.

  PMID: 31337135 BACKGROUND

• Balagura G, Iapadre G, Verrotti A, Striano P. Moving beyond sodium valproate: choosing the right anti-epileptic drug in children. Expert Opin Pharmacother. 2019 Aug;20(12):1449-1456. doi: 10.1080/14656566.2019.1617850. Epub 2019 May 17.

  PMID: 31099271 BACKGROUND

• Cavus I, Romanyshyn JC, Kennard JT, Farooque P, Williamson A, Eid T, Spencer SS, Duckrow R, Dziura J, Spencer DD. Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program. Ann Neurol. 2016 Jul;80(1):35-45. doi: 10.1002/ana.24673. Epub 2016 Jun 13.

  PMID: 27129611 BACKGROUND

• Fassi G, Igoa A, Liste OA. [Valproate-induced hyperammonemic encephalopathy. Review of cases in the psychiatric setting]. Vertex. 2008 Nov-Dec;19(82):371-7. Spanish.

  PMID: 19424520 BACKGROUND

• Deng J, Fu ZR, Wang L, Liu J, Chen CH, Fang F, Wang XL. Acute liver failure associated with lamotrigine in children with epilepsy: A report of two cases and thoughts on pharmacogenomics. Epilepsy Behav Rep. 2022 Oct 19;20:100568. doi: 10.1016/j.ebr.2022.100568. eCollection 2022.

  PMID: 36345310 BACKGROUND

• Fu J, Peng L, Wang W, He H, Zeng S, Chen TC, Chen Y. Sodium Valproate Reduces Neuronal Apoptosis in Acute Pentylenetetrzole-Induced Seizures via Inhibiting ER Stress. Neurochem Res. 2019 Nov;44(11):2517-2526. doi: 10.1007/s11064-019-02870-w. Epub 2019 Sep 11.

  PMID: 31512113 BACKGROUND

• Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila). 2009 Feb;47(2):101-11. doi: 10.1080/15563650902752376.

  PMID: 19280426 BACKGROUND

• Zhang D, Qiu L, Zhang Y, Sang Y, Zheng N, Liu X. Efficacy and safety of sodium valproate plus lamotrigine in children with refractory epilepsy. Exp Ther Med. 2020 Sep;20(3):2698-2704. doi: 10.3892/etm.2020.8984. Epub 2020 Jul 10.

  PMID: 32765764 BACKGROUND

• Moosa ANV. Antiepileptic Drug Treatment of Epilepsy in Children. Continuum (Minneap Minn). 2019 Apr;25(2):381-407. doi: 10.1212/CON.0000000000000712.

  PMID: 30921015 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Interventions

Valproic Acid; Lamotrigine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

mona M Abdellatief, M.B.B.CH

CONTACT

01124048288; mona.mohammed.@aun.edu.eg

rasha B Abd-ellatief, B.H.D

CONTACT

01003655676; rashabakheet@aun.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle investigator

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: May 31, 2023
• Study Start: July 29, 2024
• Primary Completion: July 30, 2024
• Study Completion: April 1, 2025
• Last Updated: July 30, 2024

Record last verified: 2024-07