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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Epileptic Spasms, Failed Hormonal Therapy

Intervention / Treatment
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* Other: Modified Atkins diet
* Drug: Topiramate


Participation Criteria
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Eligibility Criteria
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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 -

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 3 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: Randomized Open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modified Atkins Diet Arm<br>Modified Atkins diet will be added to the ongoing anti-seizure medication regimen | Other: Modified Atkins diet<br>* The modified Atkins diet is a less restrictive version of the ketogenic diet<br>* Other names: Ketogenic diet;|
| Active Comparator: Topiramate arm<br>Topiramate will be added to the ongoing anti-seizure medication regimen | Drug: Topiramate<br>* Topiramate is an anti-seizure medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of children with ≥ 50% reduction in clinical spasms at 12 weeks as compared to baseline as per parental reports in both groups | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 |