Efficacy Study of Folic Acid Supplementation in Adolescent Epileptics

Study Overview
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Brief Summary
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The present study is planned to study effect of folic acid supplementation on homocysteine levels and CV risk factors such as BP and lipids in adolescent epileptics taking anti-epileptic drugs (AEDs).

Detailed Description
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Scientific background, significance and impact value of the project: Homocysteine is a thiol-containing amino acid formed as an intermediate product during the methionine metabolism. Re-methylation pathway recycles Homocysteine back to methionine and requires vitamin B12 and folic acid as cofactors. [1] The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for cardiovascular (CV) disease. [2] The total homocysteine level is the lowest in children and an increase with age is higher in male sex. [2] The cutoffs for homocysteine level in adolescent range from 4.3 to 9.9 µmol/l, and hyperhomocysteinemia is defined as homocysteine >10.9 µmol/l. [3] Lower folate and higher homocysteine concentrations may put adolescent on AEDs at special risk for atherosclerosis in their adulthood. [4] This demands early intervention as Asian Indian adolescents are genetically more exposed to cadiovascular disease(CVD) risks, AED therapy is an additional risk for developing future CVDs. Adolescent epileptics on AED have to take it for long time, and homocysteine elevation itself has got epileptogenic potential and can cause the risk developing refractory epilepsy. [5] Literature search reveals several studies depicting role of vitamin B12 in regulation of blood homocysteine levels. [6, 7] However, the studies confirming role of folic acid supplementation in hyperhomocysteinemia and related CV diseases are fewer and scarce in AEDs induced hyperhomocysteinemia. Few studies have reported negative correlation between hyperhomocysteinemia and low folic acid levels in patients on AEDs. [8] At the same time few studies have reported effectiveness of folic acid supplementation to normalize the homocysteine levels. [9] Considering the results of various studies many doctors are now prescribing folic acid along with AEDs, although there is a scarcity of data from India. In this context, the present study is planned to study effect of folic acid supplementation on homocysteine levels and CV risk factors such as BP and lipids in adolescent epileptics taking AEDs.

Official Title
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Efficacy Study of Folic Acid Supplementation on Homocysteine Levels in Adolescent Epileptics Taking Antiepileptic Drugs: A Single Blind Randomized Controlled Clinical Trial

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Folic Acid
* Drug: Saccharine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed epileptic patients of either sex with age between 10-19 yrs (<19yrs), coming to the medicine Out Patient /In Patient Departments and undergoing AED therapy for more than 6 months. Epileptics with high homocysteine levels i.e. > 10.9 µmol/L (Normal homocysteine levels are 4.3-9.9 µmol/L for male and 3.3-7.2 µmol/L for female adolescent and a high homocysteine concentration is deaned as at least 11.4 µmol/L for male and at least 10.4 µmol/L for female. Gender mean of high homocysteine concentration is 10.9 µmol/L) [5] Exclusion Criteria: Pregnancy and lactation Patients with diabetes, Ischemic heart disease (IHD), stroke, malignancy and psychiatric diseases are excluded from study. The patients receiving vitamin supplements or who had clinical evidence for an acute illness, renal dysfunction, thyroid dysfunction, chronic inflammatory diseases, inborn errors of homocysteine, cobalamin or folate metabolism, or any other condition known to interfere with homocysteine metabolism will be excluded Patients who are already involved in any other trial. Patients not willing to fill consent/ assent form are also excluded from study.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 19 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Will receive Oral saccharine tablet daily for 1month along with their existing antiepileptic therapy | Drug: Saccharine<br>* Placebo group(n=12) Existing Anti-epileptic Drugs + Oral saccharine 10 mg tablet daily for 1month<br>* Other names: Sugar free;|
| Experimental: Test group<br>Will receive Oral Folic acid 1mg tablet daily for 1month along with their existing antiepileptic therapy | Drug: Folic Acid<br>* Test group(n= 24) Existing Anti-epileptic Drugs + Oral Folic acid 1mg tablet daily for 1month<br>* Other names: Folvite;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in serum homocysteine levels by 2 µmol/l |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in baseline serum lipids | Change in baseline serum lipids following Anti-epileptic therapy will be compared between placebo and test group. | 1 month | 
| Change in baseline systolic blood pressure | Change in baseline systolic blood pressure will be compared between placebo and test group. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-epileptic drugs, Folic acid, Homocysteine