Modified Atkins Diet Versus Levetiracetam for Refractory Childhood Epilepsy (LEVEMAD)

Modified Atkins Diet Versus Levetiracetam for Refractory Epilepsy in Children: A Randomized Open-Label Study

In this study, the efficacy of add-on modified Atkins diet will be compared with add-on Levetiracetam in children with refractory epilepsy in a randomized open label trial. The results will aid clinicians in deciding the treatment options when a child has been diagnosed to have refractory epilepsy.

Study Overview

• Status: Unknown
• Conditions: Refractory Childhood Epilepsy
• Intervention / Treatment: Other: Modified Atkins Diet; Drug: Levetiracetam

Detailed Description

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate seizures and by the neurobiologic, cognitive, psychological and social consequences of this condition. Epilepsy is a disabling and common neurological condition which rank 4th in the world's neurological disorder burden, which can be controlled successfully in most of the patients with one or more antiepileptic drugs. But approximately 30% of patients with epilepsy have refractory epilepsy, which is, a failure to respond to adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules to achieve sustained relief of seizures.Many severe and catastrophic epilepsies present in children such as West syndrome, Lennox Gastaut syndrome, Dravet syndrome. Uncontrolled epilepsy carries significant risks for the affected child, such as injuries, cognitive and behavioural problems. Epilepsy surgery is a good option but it is expensive and not easily available. Also, many children with refractory epilepsy are not good surgical candidates. Hence there is a need to consider alternative treatments in these children.

The ketogenic diet is an individually calculated and rigidly controlled high-fat, low carbohydrate diet used for the treatment of difficult to control seizures. The ketogenic diet is an effective treatment option for refractory childhood epilepsy however it is very restrictive and difficult to implement in low resource settings. The modified Atkins diet is a less restrictive alternative to the traditional ketogenic diet. This diet is started on an outpatient basis without a fast, and allows unlimited protein and fat. This diet has been shown to be equally effective as the ketogenic diet and a useful option in resource-constraint settings. The modified Atkins diet has been demonstrated to be effective in refractory childhood epilepsy in two randomized controlled trials from India. However, in both these trials the control groups continued their ongoing antiepileptic medication without any new treatment.

Levetiracetam is one of the newer antiepileptic drugs available for treating drug resistant epilepsy. It is a broad-spectrum antiepileptic drug effective in most seizure types. It also has an excellent pharmacokinetics and tolerability profile with no known pharmacokinetic interactions. Use of levetiracetam as an add on drug in refractory childhood epilepsy recently in some published studies has shown good efficacy.

In this study, the efficacy of add-on modified Atkins diet will be compared with add-on Levetiracetam in children with refractory epilepsy in a randomized open label trial. The results will aid clinicians in deciding the treatment options when a child has been diagnosed to have refractory epilepsy.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Suvasini Sharma; Phone Number: 91 9910234344; Email: sharma.suvasini@gmail.com
• Study Contact Backup: Name: Sharmila B Mukherjee; Phone Number: 91 9818159699; Email: theshormi@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110018
      • Recruiting
      • Lady Hardinge Medical College
      • Contact: Suvasini Sharma, MD DM; Phone Number: 91 9910234344; Email: sharma.suvasini@gmail.com
      • Contact: Sharmila B Mukherjee, MD; Phone Number: 91 9818158699; Email: sharma.suvasini@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Seizures persisting more than 3 per week despite the use of at least 2 appropriate anti-epileptic drugs in appropriate doses -

Exclusion Criteria:

1. Known or suspected inborn error of metabolism
2. Surgically remediable causes of epilepsy such as tumours, cortical dysplasia, mesial temporal lobe epilepsy etc with refractory focal epilepsy.
3. Prior use of the ketogenic or modified Atkins diet or levetiracetam.
4. Systemic illness- chronic hepatic, renal or pulmonary disease

5. Prior history of depression or severe behavioural problems.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified Atkins Diet; Modified Atkins Diet administration; Carbohydrates will be restricted to 10 grams per day.; Recipes will be provided to be prepared from easy home available foods, to have 2.5 gram per meal. Along with this, a list of carbohydrate free foods will be provided.; Fats intake will be actively encouraged. Protein intake will be unrestricted.; Medications will be changed to carbohydrate free preparations.; A multivitamin and calcium supplementation will be added.	Other: Modified Atkins Diet; Modified Atkins diet is a type of ketogenic diet which is less restrictive; Other Names: Ketogenic Diet subtype
Active Comparator: Levetiracetam; Levetiracetam will be started at a dose of 10 mg/kg/day in two divided doses and increased to 20 mg/kg/day after 1 week. Syrups will be used in children younger than 5 years of age, and tablets will be used in children > 5 years of age. Further dose titration will be done as per the seizure control, in 10 mg/kg/day increments in 2 weekly intervals, to a maximum of 60mg/kg/day.	Drug: Levetiracetam; Levetiracetam is a second generation anti-epileptic drug which is broad spectrum and commonly used as add-on in refractory epilepsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy in reducing seizures measured by The proportion of responders, i.e., patients who achieve > 50% seizure reduction from the baseline in the modified Atkins diet group at 3 months in comparison to the levetiracetam group.	The proportion of responders, i.e., patients who achieve > 50% seizure reduction from the baseline in the modified Atkins diet group at 3 months in comparison to the levetiracetam group.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent adverse effects in both groups	Tolerability and the adverse effects of the modified Atkins diet and levetiracetam	3 months

Collaborators and Investigators

• Sponsor: Lady Hardinge Medical College

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2019
• Primary Completion (Anticipated): March 31, 2021
• Study Completion (Anticipated): April 20, 2021

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 19, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: LEVEMAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No