Comparison of Efficacy of LGIT and MAD Among Children With Drug Resistant Epilepsy

Study Overview
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Brief Summary
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To compare the efficacy of two less restrictive dietary therapies - LGIT and MAD, used for treatment of drug resistant epilepsy in children

Detailed Description
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Up to one third of patients with epilepsy progress to drug resistant epilepsy (DRE). Current treatment options for DRE include epileptic surgery and dietary therapy. Classic KD (Ketogenic diet) is the most studied dietary therapy but the stringent restrictions and practical difficulty makes it difficult to follow. So less restrictive diets like MAD and LGIT were introduced. These are reported to have less adverse effects also. But no published study has ever been conducted comparing these two diets head to head.

Official Title
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Comparison of Efficacy of Low Glycemic Index Therapy and Modified Atkins Diet Among Children With Drug Resistant Epilepsy: A Randomized Non-inferiority Trial

Conditions
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Drug Resistant Epilepsy, Ketogenic Dieting

Intervention / Treatment
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* Other: Low glycemic Index Therapy (LGIT)
* Other: Modified Atkins Diet (MAD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 1-15 years with drug resistant epilepsy Willing to come for regular follow-up according to study protocol Drug resistant epilepsy defined as Seizure frequency >4 seizures per month, while on optimal doses of at least 2 prescribed antiepileptic drugs For West syndrome, drug resistant epilepsy will be defined as more than 4 clusters of spasms per month despite treatment with antiepileptic drugs and either ACTH(Adrenocorticotrophic hormone) or Vigabatrin Exclusion Criteria: Surgically remediable causes for DRE Inborn errors of metabolism Previously received KD, MAD or LGIT Known case of Chronic kidney disease Chronic liver disease/GI illness Congenital/acquired heart disease Chronic respiratory illness

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 15 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: Open label randomized non inferiority trial with two parallel arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Glycemic Index therapy<br>Specific dietary therapy called Low glycemic Index Therapy (LGIT) which provides diet including food items with glycemic index less than 50 only | Other: Low glycemic Index Therapy (LGIT)<br>* Specific dietary therapy called Low glycemic Index Therapy (LGIT) which provides diet including food items with glycemic index less than 50 only. For this purpose, various dietary menus will be provided to the parents.<br>|
| Active Comparator: Modified Atkins Diet<br>Specific dietary therapy called Modified Atkins Diet (MAD) which provides diet with restricted carbohydrates upto 20 grams per day and increased fat and protein ratio | Other: Modified Atkins Diet (MAD)<br>* Specific dietary therapy called Modified Atkins Diet (MAD) which provides diet with restricted carbohydrates upto 20 grams per day and increased fat and protein ratio. For this purpose, various dietary menus will be provided to the parents.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of seizure reduction from baseline at 24 weeks of therapy | Mean weekly seizure reduction at 24 weeks divided by Mean weekly seizure measured at baseline multiplied by 100 | At the end of 24 weeks of dietary therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children who achieve >50% seizure reduction | Number of children with >50% reduction divided by number of children in each arm | At the end of 24 weeks of dietary therapy | 
| Incidence of adverse events | Routine hemogram, Renal function test (RFT), Liver function test (LFT) and lipid profile will be assessed for any alterations. Adverse events, vomiting, constipation and diarrhea will be checked by parents record | At the end of 24 weeks of dietary therapy | 
| Compliance of participants with dietary therapy in each arm will be determined each week, whether satisfactory or unsatisfactory | Weekly compliance assessment of each participant will be done | At the end of 24 weeks of dietary therapy | 
| Change in Social quotient(SQ) with each dietary therapies | Proportion of children with improvement in Social quotient (SQ) assessed by Vineland Social Maturity Scale (VSMS) at 24 weeks. VSMS consists of 8 subsets - Communication skills, General self-help ability, Locomotion skills, Occupation skills, Self-direction, Self-help eating, Self-help dressing, Socialization skills. Social age is calculated by adding the scores of all subsets. Social quotient (SQ) is calculated by social age divided by chronological age multiplied by 100. | At the end of 24 weeks of dietary therapy | 
| Change in Quality of Life of participants who are less than 4 years of age at 24 weeks as compared to baseline | In children less than 4 years quality of life is assessed by PedsQL (Pediatric Quality of life inventory). PedsQL consists of 21 questions each having 5 responses with scores 0,1,2,3 and 4. Minimum score is 0 and maximum is 84. Quality of life is poor with larger score. | At the end of 24 weeks of dietary therapy | 
| Change in Quality of Life of participants who are more than or equal to 4 years of age at 24 weeks as compared to baseline | In children with age 4 years or more, QOLCE 55 (Quality of life in childhood epilepsy questionnaire) is used to assess quality of life. QOLCE 55 consists of 55 questions which are classified into 4 categories. Each question have 5 responses with scores as 0,25,50,75 and 100. Mean score of each category is calculated and final score calculated by mean of the scores of 4 categories. Minimum score is 0 and maximum is 100. Quality of life is better with larger score. | At the end of 24 weeks of dietary therapy | 
| Change in Quality of Life of caregivers at 24 weeks as compared to baseline | Quality of life of caregivers is assessed by WHOQOL-BREF. WHOQOL BREF contains 26 items categorized into 4 domains. For each question response is scored 1,2,3,4 or 5. Total raw score is then calculated and is converted to transformed score. Minimum score is 0 and maximum is 100. Quality of life is poor with smaller score. | At the end of 24 weeks of dietary therapy | 
| Gut microbiota (GM) analysis pre and post dietary therapy | Changes in percentage distribution of various micro organisms in gut microbiota after dietary therapy as compared to baseline GM | At the end of 24 weeks of dietary therapy | 
| Change in behavioral abnormalities with each dietary therapy | Behavior assessment is done using Child behavior check list (CBCL).This questionnaire contains 100 and 113 questions for age groups of 1 ½ - 5 years and 6-18 years respectively. Score of 2 will be given for a response of 'very true', 1 for a response of 'somewhat true' and 0 for 'not true'. Total score is obtained by adding all the subsets. Subsets for age 1.5 years to 5 years include - Emotionally reactive, anxious/depressed, somatic complaints, withdrawn, sleep problems, attention problems, aggressive behavior and other problems. Subsets for age 6 years to 12 years include - Anxious/Depressed, withdrawn, somatic complaints, social problems, thought problems, attention problems, rule breaking behavior, aggressive behavior, other problems. Raw score is then converted to T score according to the published charts. Minimum T score is 28 and maximum is 100. Larger score indicates more behavioral problems. | At the end of 24 weeks of dietary therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MAD, LGIT