The Role of Vitamin D in Neuroinflammatory on Drug Resistant Epilepsy

Study Overview
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Brief Summary
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The incident of epilepsy still very high in Indonesia, thus many patients become drug resistant epilepsy. As vitamin D has some anticonvulsant effect, the investigators want to study if an additional dose of vitamin D can help with the therapy responses.

Detailed Description
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Specifically the investigators want to study about : Correlation between serum vitamin D levels and seizure frequency change after vitamin D treatment Correlation between serum GDNF levels and seizure frequency change after vitamin D treatment Correlation between serum Interleukin-1ß levels and seizure frequency change after vitamin D treatment Responder rate. Percentage of patients change of at least 50% of the seizure frequency Remission rate after vitamin D treatment. Percentage of patients without any seizure (seizure freedom) Effect of vitamin D according to epilepsy type. Responder rate in focal and generalized epilepsy. Effect on Global Assesment of the Severity of Epilepsy (GASE) Effect on Hague Seizure Severity scale (HASS) Effect on Quality of Life in Epilepsy in Children: (QOLCE 55)

Official Title
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The Role Of Vitamin D For Therapy Responses On Drug Resistant Epilepsy Through Glial-Cell-Line Derived Neurotrophic Factor (GDNF) And Interleukin 1ß (IL-1 ß) Modulation Pathway

Conditions
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Drug Resistant Epilepsy

Intervention / Treatment
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* Drug: Cholecalciferol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 1 - 18 years Drug-resistant epilepsy Having at least 6 unprovoked seizures in the previous 3 months No vitamin D treatment in the previous 6 months Medication compliance Agreeing to participate in the study Having a social insurance Parental agreement Exclusion Criteria: Treatments influencing the metabolism of vitamin D other than anticoagulants (rifamycin, isoniazid, ketoconazole, 5-FU fluorouracil, leucovorin) Known hypersensitivity to vitamin D Lost to follow up

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>DRE patients with proved vitamin D deficiency (Serum vitamin D level <30ng/ml). intervention: Daily Cholecalciferol 1000 IU in 24 weeks. | Drug: Cholecalciferol<br>* Daily Cholecalciferol 1000 IU in 24 weeks<br>* Other names: Vitamin D;|
| Placebo Comparator: Placebo<br>DRE patients with proved vitamin D deficiency (Serum vitamin D level <30ng/ml). Interventions: Daily Placebo oral (Manufactured to mimic Cholecalciferol) in 24 weeks. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change of seizure frequency | Change on number of seizure | 12 and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between serum vitamin D levels and seizure frequency change after vitamin D treatment | The vitamin D levels (in ng/mL) of each participant is measured at the beginning and the end of the study and then the investigators calculate the seizure frequency change (in percentage, %) | 12 and 24 weeks | 
| Correlation between serum GDNF levels and seizure frequency change after vitamin D treatment | The serum GDNF levels (in ng/mL) of each participant is measured at the beginning and the end of the study and then the investigators calculate the seizure frequency change (in percentage, %) | 12 and 24 weeks | 
| Correlation between serum Interleukin-1ß levels and seizure frequency change after vitamin D treatment | The serum Interleukin-1ß levels (in ng/mL) of each participant is measured at the beginning and the end of the study and then the investigators calculate the seizure frequency change (in percentage, %) | 12 and 24 weeks | 
| Responder rate | Percentage of patients change at least 50% of the seizure frequency | 12 and 24 weeks | 
| Remission rate after vitamin D treatment | Percentage of patients without any seizure (seizure freedom) | 12 and 24 weeks | 
| Effect of vitamin D according to epilepsy type | Responder rate in focal and generalized epilepsy | 12 and 24 weeks | 
| Effect on Global Assessment of the Severity of Epilepsy (GASE) | Effect on Global Assessment of the Severity of Epilepsy (GASE) will be performed at beginning and the end of the study with 7 point Likert in which options are 1 = Not at all severe, 2 = A little severe, 3 = Somewhat severe, 4 = Moderately severe, 5 = Quite severe, 6 = Very severe, 7 = Extremely severe. | 12 and 24 weeks | 
| Effect on Hague Seizure Severity scale (HASS) | The Hague Seizure Severity scale (HASS) will be performed at beginning and the end of the study with minimum score = 13 to maximum score = 54, in which the lower score indicates the lowest level of seizure severity | 12 and 24 weeks | 
| Effect on Quality of Life in Epilepsy in Children: (QOLCE 55) | Effect on Quality of Life in Epilepsy in Children: (QOLCE 55) will be performed at beginning and the end of the study with 5 points in which options are 1 = Poor, 2 = Fair, 3 = Good, 4 = Very good, 5 = Excellent. | 12 and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, GDNF, interleukin