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

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.

Study Overview

• Status: Recruiting
• Conditions: Epileptic Spasms, Failed Hormonal Therapy
• Intervention / Treatment: Other: Modified Atkins diet; Drug: Topiramate

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 Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Suvasini Sharma, MD, DM; Phone Number: 0091 9910234344; Email: sharma.suvasini@gmail.com
• Study Contact Backup: Name: Sharmila B Mukherjee, MD; Phone Number: 0091 9818158699; Email: theshormi@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110001
      • Recruiting
      • Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital
      • Contact: Suvasini Sharma, DM; Email: sharma.suvasini@gmail.com
      • Sub-Investigator: Suvasini Sharma, DM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

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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

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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 Arm; Modified Atkins diet will be added to the ongoing anti-seizure medication regimen	Other: Modified Atkins diet; The modified Atkins diet is a less restrictive version of the ketogenic diet; Other Names: Ketogenic diet
Active Comparator: Topiramate arm; Topiramate will be added to the ongoing anti-seizure medication regimen	Drug: Topiramate; Topiramate is an anti-seizure medication

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Lady Hardinge Medical College
• Investigators: Principal Investigator: Suvasini Sharma, MD, DM, Lady Hardinge Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Estimated): July 24, 2023

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: TOPAMAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No