Clinical trial NCT05881928: Effect of Adding Lamotrigine to Sodium Valproate in Childhood Epilepsy: Clinicolabratory Study
Official title: Effect of Adding Lamotrigine to Sodium Valproate in Childhood Epilepsy: Clinicolabratory Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Epilepsy
Lamotrigine
Sodium Valproate Adverse Reaction
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2023-05-31
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed description: Epilepsy is one of the most common serious chronic brain disorders of childhood. It is characterized by recurrent seizures that can cause motor, sensory, cognitive, psychic, or autonomic disturbances. It has a negative impact on 0.6% of the population in developed countries and 1.6% in developing countries . 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 . Although the treatment for RE has been continuously updated, the exploration of high efficacy AED combinations is still ongoing . 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 , and also has the function of resisting depression and stabilizing mood . It is applicable for children and adolescents with various seizure types and syndromes due to its good anticonvulsant, tolerance, broad spectrum activity, and safety . 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) has also been mentioned as a rare hypersensitivity reaction . 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, Investigators will add lamotrigine for 6 months. Setting: single -center study with outpatient from University Children's Hospital , Faculty of Medicine , Assuit University Design of this study :- Cross -sectional interventional. Selected patient for this study will receive additional treatment of LTG with SV for 6 month .

Doses of the drugs: Sodium valproate : 30 mg / kg / day , maximum dose 1500mg / day . LTG will be initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses, followed by 1.0 mg/kg/day for an additional 2 weeks,followed by 1.5mg/kg/day for additional 2weeks Thereafter, doses will be increased in 0.5mg/kg/day increments every 2weeks until intolerable adverse effects occurred, or a maximum dose of 3mg/kg/day will be reached .

The outcome measures :

The outcome measures will be . 1.Clinical measures: -patient will be clinically examined For side effects(body weight ,muscle weakness ,ataxia , hair loss). - The seizure frequency before and after adding lamotrigine. the investigators will exclude patient with allergy to LTG after the first 2 weeks of treatment.

2- Laboratory measures :- -Serum concentration of lamotrigine at the end of study . - The incidence of adverse reactions will be assessed by lab tests as 1. liver function tests. 2.serum ammonia 3. coagulation function 4. complete blood count. 3-Neurophysological evaluation:-EEG will be done at the beginning and end of the study.

Inclusion criteria : 1. Male or female, ages 2 - 12years.

2 . 50 epileptic children on sodium valproate for 6 months without complete remission.

Exclusion Criteria:

Subjects will be excluded if any of the following criteria are met:-

1. Suspected other neurological disorders .
2. Allergic to LTG.
3. Liver dysfunction.
4. kidney dysfunction .
5. Not cooperating with this study

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Weight
timeFrame: 6 months
Secondary outcomes:
measure: liver function tests
timeFrame: 6months
measure: serum ammonia.
timeFrame: 6months
measure: complete blood count
timeFrame: 6 months
measure: E.E.G
timeFrame: 6months
measure: Serum concentration of LTG
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
References:
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