Dietary Therapy In Epilepsy Treatment (DIET-Trial): A Randomised Non Inferiority Trial Comparing KD, MAD & LGIT for Drug Resistant Epilepsy

Not Applicable

• Conditions: Drug Resistant Epilepsy
• Interventions: Other: MAD; Other: Ketogenic Diet; Other: LGIT

• Registration Number: NCT02708030
• Lead Sponsor: All India Institute of Medical Sciences, New Delhi

Brief Summary

This randomised trial is undertaken to assess whether MAD or LGIT is non-inferior to KD with regard to seizure control at twenty-four weeks among children with drug resistant epilepsy. The hypothesis of the study is that in 1 to 15-year-old children with drug resistant epilepsy, use of Modified Atkins Diet (MAD) or Low Glycemic Index Therapy (LGIT) as an add on to the ongoing anti-epileptic drugs would not be inferior to ketogenic diet by \>15% in terms of seizure reduction from baseline seizure frequency at 24 weeks.

The primary outcome of the study is to determine the efficacy of MAD as compared to KD and LGIT as compared to KD for seizure reduction in drug resistant epilepsy following 24 weeks of dietary therapy in 1 to 15-year-old children on anti-epileptic drugs. The change in seizure frequency will be estimated as percentage change in seizure reduction at 24 weeks as compared to baseline.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-02-22
• Study First Submitted QC: 2016-03-09
• Study First Posted: 2016-03-15
• Study Start: 2016-04
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-13
• Last Update Posted: 2017-07-17
• Primary Completion: 2017-08
• Study Completion: 2017-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

1. Children aged 1-15 years with drug resistant epilepsy (Drug resistant epilepsy for the study will be defined as seizure frequency >4 seizures per month, and treatment failure of ≥2 prescribed antiepileptic drugs).
2. Willing to come for regular follow up

Exclusion Criteria

1. Surgically remediable cause for drug resistant epilepsy

2. Proven inborn error of metabolism except those in which KD is indicated (i.e., Pyruvate Carboxylase deficiency and GLUT-1 Deficiency)

3. Previously received KD, MAD or LGIT

4. Known case of

   1. Chronic kidney disease
   2. Chronic liver disease/ GI illness
   3. Chronic heart disease (congenital and acquired)
   4. Chronic respiratory illness

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Modified Atkins Diet	MAD	Modified Atkins Diet (MAD) will be administered on out patient basis. Parents of children will be advised to monitor for seizure frequency and ketosis at home.
Ketogenic Diet	Ketogenic Diet	Ketogenic diet (KD) will be administered by the non-fasting protocol. The child will be admitted to the hospital, and KD will be started in 1:1 ratio. The ratio will increased every 48hours to a maximum of 4:1 or ketosis (urinary ketones 40-80mg/dL) is attained. The child will thereafter be discharged and followed up on Out patient basis.
Low Glycemic Index Therapy	LGIT	Low Glycemic Index Therapy (LGIT) will be administered on out patient basis. Parents of children will be advised to monitor for seizure frequency and ketosis at home.

Primary Outcome Measures

Name	Time	Method
Percentage change in seizure frequency after 24 weeks of dietary therapy as compared to baseline, in the arm KD as compared to MAD and in the arm KD as compared to LGIT	Baseline and six months	Percentage change in seizure frequency will be estimated as mean number of weekly seizures over preceding 4 weeks after 24 weeks of dietary therapy divided by mean number of weekly seizures over preceding 4 weeks at the baseline.; It will be calculated for each of the three arms (KD; MAD; LGIT) and KD will compared to MAD and LGIT individually as the primary outcome.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients who achieve >50% seizure reduction from baseline at 24 weeks after diet initiation	Baseline and twenty-four weeks	Proportion of patients who achieve \>50% seizure reduction from baseline at 24 weeks after diet initiation
Evaluate GI adverse events (diarrhoea, constipation and vomiting) assessed by parental questionnaire in each of the three arms at baseline and six months after therapy	Baseline and twenty-four weeks
Estimate behavior change as measured by Childhood behavior checklist in each of three arms at baseline, 12 weeks and 24 weeks after dietary therapy	Baseline, twelve weeks, and twenty-four weeks
Evaluate change in serum levels of micronutrients by laboratory testing in each of three arms at baseline and six months after therapy	Baseline and twenty-four weeks	Micronutrients like copper, zinc, retinol and vitamin E would be compared
Evaluate omega3 polyunsaturated fatty acid levels and correlate it with change in seizure frequency	Baseline and twenty-four weeks
Percentage change in seizure frequency after 24 weeks of dietary therapy as compared to baseline, in the arm MAD as compared to LGIT	Baseline and twenty-four weeks	Percentage change in seizure frequency will be estimated as mean number of weekly seizures over preceding 4 weeks after 24 weeks of dietary therapy divided by mean number of weekly seizures over preceding 4 weeks at the baseline. Change in seizure frequency in MAD and LGIT arm will be compared
Estimate cognition change as assessed by Vineland Social Maturity Scale in each of three arms at baseline, 12 weeks and 24 weeks after dietary therapy	Baseline and twenty-four weeks

Trial Locations

Locations (1)

All India Institute of Medical Sciences; 🇮🇳 New Delhi, Delhi, India