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

NCT02708030 | Unknown

• 1 other identifier: KD Vs MAD Vs LGIT
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Resistant Epilepsy

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Baseline and six months

Secondary Outcomes (7)

• 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

• Proportion of patients who achieve >50% seizure reduction from baseline at 24 weeks after diet initiation

  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

• 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

• 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

Study Arms (3)

Ketogenic Diet

ACTIVE COMPARATOR

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.

Other: Ketogenic Diet

Modified Atkins Diet

EXPERIMENTAL

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.

Other: MAD

Low Glycemic Index Therapy

EXPERIMENTAL

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.

Other: LGIT

Interventions

Ketogenic Diet OTHER

The children with the drug resistant epilepsy will go through a run in period of 4 weeks during which each child will undergo a detailed detailed clinical evaluation according to a structured proforma, and baseline investigations. The patients in KD arm will be admitted to the hospital for initiation of diet.

Ketogenic Diet

MAD OTHER

The children with the drug resistant epilepsy will go through a run in period of 4 weeks during which each child will undergo a detailed detailed clinical evaluation according to a structured proforma, and baseline investigations. Following the run in period of 4 weeks, the patients will be randomized to the MAD or LGIT or KD arm. MAD will be initiated on out patient basis.

Modified Atkins Diet

LGIT OTHER

The children with the drug resistant epilepsy will go through a run in period of 4 weeks during which each child will undergo a detailed detailed clinical evaluation according to a structured proforma, and baseline investigations. Following the run in period of 4 weeks, the patients will be randomized to the MAD or LGIT or KD arm. LGIT will be initiated on out patient basis.

Low Glycemic Index Therapy

Eligibility Criteria

• Age: 1 Year - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• Willing to come for regular follow up

You may not qualify if:

• Surgically remediable cause for drug resistant epilepsy
• Proven inborn error of metabolism except those in which KD is indicated (i.e., Pyruvate Carboxylase deficiency and GLUT-1 Deficiency)
• Previously received KD, MAD or LGIT
• Known case of
• Chronic kidney disease
• Chronic liver disease/ GI illness
• Chronic heart disease (congenital and acquired)
• Chronic respiratory illness

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (1)

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Related Publications (2)

• Sondhi V, Agarwala A, Pandey RM, Chakrabarty B, Jauhari P, Lodha R, Toteja GS, Sharma S, Paul VK, Kossoff E, Gulati S. Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial. JAMA Pediatr. 2020 Oct 1;174(10):944-951. doi: 10.1001/jamapediatrics.2020.2282.

  PMID: 32761191 DERIVED

• Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Jun 24;6(6):CD001903. doi: 10.1002/14651858.CD001903.pub5.

  PMID: 32588435 DERIVED

MeSH Terms

Conditions

Drug Resistant Epilepsy

Interventions

Diet, Ketogenic; mycophenolic adenine dinucleotide

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 15, 2016
• Study Start: April 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: September 1, 2017
• Last Updated: July 17, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

IN (1)