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

Lady Hardinge Medical College

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Epileptic Spasms, Failed Hormonal Therapy

Treatments: Other: Modified Atkins diet; Drug: Topiramate

Study type: Interventional

Funder types: Other

Identifiers

NCT05958160

TOPAMAD

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 estimated patients

Sex: All

Ages: 9 months to 3 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Modified Atkins Diet Arm

Experimental group

Description:

Modified Atkins diet will be added to the ongoing anti-seizure medication regimen

Treatment:

Other: Modified Atkins diet

Topiramate arm

Active Comparator group

Description:

Topiramate will be added to the ongoing anti-seizure medication regimen

Treatment:

Drug: Topiramate