Modified Atkins Diet Versus Topiramate In Children With Epileptic Spasms Refractory To Hormonal Treatment: A Randomized Open-Label Study

Phase 2

Recruiting

• Conditions: Epileptic Spasms, Failed Hormonal Therapy
• Interventions: Other: Modified Atkins diet; Drug: Topiramate

• Registration Number: NCT05958160
• Lead Sponsor: Lady Hardinge Medical College

Brief Summary

This study has been planned to compare the efficacy and tolerability of topiramate, a commonly used second line agent, with modified Atkins diet in children with epileptic spasms refractory to hormonal treatment, in a randomized open label study.

Detailed Description

Infantile epileptic spasms syndrome, formerly known as West syndrome is a severe and difficult to treat epilepsy syndrome in infants and young children. The first-line options of this condition include hormonal therapy, i.e., adrenocorticotropic hormone (ACTH) or oral corticosteroids, and/or vigabatrin. These are effective in 45%-55% of the patients. These are however associated with significant side effects, and high relapse rates. Newer drugs such as topiramate, zonisamide, and levetiracetam have also been evaluated; but there have been no randomized trials to evaluate the efficacy of these agents. Topiramate is one of the most commonly used second line agents used for the treatment of epileptic spasms.

The ketogenic diet (KD), a high-fat, low-carbohydrate, adequate-protein diet is an established, effective non-pharmacologic treatment for children with intractable epilepsy. Despite being highly efficacious, ketogenic diet has practical constraints in implementation leading to need for alternative approaches. The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is more palatable and acceptable in comparison to ketogenic diet. The modified Atkins diet has shown to be effective in children with epileptic spasms refractory to first line treatment in a recent randomized controlled trial, comparing add-on diet versus continuing the on-going anti-seizure medications alone. At the end of 4 weeks, 11 children in the diet group were spasm free compared with none in the control group (P ≤ .001).

This study has been planned to compare the efficacy and tolerability of topiramate, a commonly used second line agent, with modified Atkins diet in children with epileptic spasms refractory to hormonal treatment, in a randomized open label study. The results will guide clinicians as to the best options in children with epileptic spasms refractory to hormonal treatment.

Study Timeline

• Status Verified: 2023-07
• Study First Submitted: 2023-07-14
• Study First Submitted QC: 2023-07-14
• Last Update Submitted: 2023-07-14
• Study Start: 2023-07-20
• Study First Posted: 2023-07-24
• Last Update Posted: 2023-07-24
• Primary Completion: 2024-09-30
• Study Completion: 2024-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Age: 9 months to 3 years 2) Diagnosis of infantile epileptic spasms syndrome as per the ILAE 2022 diagnostic criteria 3) Failure of hormonal therapy, i.e. oral prednisolone or ACTH

Exclusion Criteria

1. Known or suspected inborn error of metabolism 2) Prior use of the ketogenic or modified Atkins diet or Topiramate 3) Systemic illness- chronic hepatic, renal or pulmonary disease 4) Diagnosed renal stones

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Modified Atkins Diet Arm	Modified Atkins diet	Modified Atkins diet will be added to the ongoing anti-seizure medication regimen
Topiramate arm	Topiramate	Topiramate will be added to the ongoing anti-seizure medication regimen

Primary Outcome Measures

Name	Time	Method
The proportion of children with ≥ 50% reduction in clinical spasms at 12 weeks as compared to baseline as per parental reports in both groups	12 weeks	The proportion of children with ≥ 50% reduction in clinical spasms at 12 weeks as compared to baseline as per parental reports in both groups

Secondary Outcome Measures

Name	Time	Method
The proportion of children with ≥ 1 point improvement in BASED score at 12 week as compared to baseline in both groups	12 weeks
Adverse effects of the intervention in both groups	12 weeks
The proportion of children with clinical spasm cessation as per parental reports at the end of 12 weeks of treatment in both groups.	12 weeks

Trial Locations

Locations (1)

Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital; 🇮🇳 New Delhi, Delhi, India