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

July 20, 2023 updated by: Mona Mohammed Abdellatief, Assiut University

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 50 epileptic patients receive SV for 6 months , for whom add lamotrigine for 6 month
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
sodium valproate tablet30 mg / kg / day , maximum 1500mg / day . LTG :
Drug: Lamotrigine
lamotrigine tablet 0.5 mg/kg for 2 weeks in two divided doses , increased in 0.5mg/kg/day increments every 2weeks .
Device: E.E.G
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weight
Time Frame: 6 months
Weight in kilogramme will be measured in 50 participants
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
liver function tests
Time Frame: 6months
blood tests that measure different enzymes, proteins, and other substances made by the liver.The liver function tests typically include alanine transaminase (ALT) and aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), serum bilirubin, prothrombin time (PT), the international normalized ratio (INR), total protein and albuminALT. 7 to 55 units per liter (U/L) AST. 8 to 48 U/L. ALP. 40 to 129 U/L. Albumin. 3.5 to 5.0 grams per deciliter (g/dL) Total protein. 6.3 to 7.9 g/dL. Bilirubin. 0.1 to 1.2 milligrams per deciliter (mg/dL) GGT. 8 to 61 U/L. LD. 122 to 222 U/L.
6months
serum ammonia.
Time Frame: 6months

An ammonia test measures the amount of ammonia in the blood , Ammonia level normal range is usually :

170-340 mcg/dL in new-borns, 70-135 mcg/dL in children , Ammonia Colorimetric Assay Kit will be used for assessment of serum ammonia levels
6months
complete blood count
Time Frame: 6 months
complete blood count, or CBC, is a blood test that measures many different parts and features of blood, including red blood cells, white blood cells, and platelets
6 months
E.E.G
Time Frame: 6months
E.E.G power in alpha band ,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 doctorisThe most commonly studied waveforms include delta (0.5 to 4Hz); theta (4 to 7Hz); alpha (8 to 12Hz); sigma (12 to 16Hz) and beta (13 to 30Hz). In addition, there are other waveforms such as infra slow oscillations (ISO) (less than 0.5Hz) and high-frequency oscillations (HFOs) (greater than 30Hz) which are outside the conventional bandwidth of clinical EEG but have recently found clinical importance with the adven
6months
Serum concentration of LTG
Time Frame: 6 months
The serum concentration should be interpreted in the context of the patient's clinical response and may provide useful information in patients showing poor response, noncompliance, or adverse effects, particularly when lamotrigine is coadministered with other epileptic drugs.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 25, 2023

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

March 21, 2023

First Submitted That Met QC Criteria

May 20, 2023

First Posted (Actual)

May 31, 2023

Study Record Updates

Last Update Posted (Actual)

July 21, 2023

Last Update Submitted That Met QC Criteria

July 20, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • lamotrigine , sodium valproate

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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