Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies

Phase 1 Study of Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies

Epileptic spasms (ES) are a predominantly infantile seizure type observed frequently in certain genetic disorders. Ketogenic diet (high ratio of fat to carbohydrate/protein) is an established non-medication treatment for difficult to control seizures, including ES. Because ES are associated with worse developmental and cognitive outcomes if not detected or treated quickly and effectively, this trial aims to test the ketogenic diet to prevent ES in this high-risk population. This trial is a single-center pilot study of 10 infants with genetic seizure disorders to establish if the protocol of early ketogenic diet administration and ES evaluation is safe and feasible.

Study Overview

• Status: Recruiting
• Conditions: Epileptic Spasms; Developmental and Epileptic Encephalopathies; Genetic Epilepsy; Neonatal and Infant Epilepsy
• Intervention / Treatment: Drug: Ketogenic diet

Detailed Description

Epileptic spasms (ES) are a highly prevalent and often refractory form of seizures in genetic Developmental and Epileptic Encephalopathies (DEEs), affecting 55% of patients. Prevalence is higher in subsets such as CDKL5 Deficiency Disorder (82%). Infantile epileptic spasms syndrome can be associated with developmental regression, and early and effective treatment of ES impacts developmental outcomes. Diagnosis of ES, made by a combination of clinical history and EEG, can be delayed if ES are subtle or mixed with other seizure patterns. Clinical experience and the literature support use of the ketogenic diet for refractory epilepsy in infancy, including ES, particularly for some established genetic diagnoses. Further, there is precedent for preventing seizures, including ES, in Tuberous Sclerosis Complex with vigabatrin. The hypothesis of this investigation is that treatment of infants with genetic DEEs with the ketogenic diet will prevent the development of ES, or, if ES do develop, improve treatment response to standard therapy. The focused goal of this proposal is to demonstrate feasibility of initiating and maintaining ketogenic diet in infants with genetic DEEs, with serial EEG monitoring. This trial is a prospective, open-label treatment with ketogenic diet (goal ratio 4:1) in 10 infants with genetic DEE (seizure onset <6 months). The trial will evaluate adherence to ketogenic diet, starting within 6 weeks of enrollment, with a primary endpoint of maintaining a minimum ratio of 1:1 through 3 months after ES onset (12 months of age if they do not develop ES). The trial will evaluate adherence to EEG testing every 6 weeks. This work will lay the foundation for a multi-center Phase 2 trial.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Heather E Olson, MD, MS; Phone Number: 617-355-7970; Email: Heather.Olson@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Jessica Landers, MS; Phone Number: 617-355-0578; Email: jessica.landers@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Plan for initiation of ketogenic diet by clinical team for treatment of epilepsy
• The clinical team initiating the ketogenic diet agrees that the use of the KetoVie formula is appropriate for the subject, as all study subjects need to receive the same formula
• Male or female, age 0 to less than 9 months (including neonates per investigator's judgment)
• Epilepsy onset at less than 6 months of age
• Abnormal development (any sub score of the Bayley-4 less than 1 standard deviation below the mean) and/or neurologic exam (microcephaly, macrocephaly, strabismus, abnormal vision/CVI, hypotonia, spasticity, dystonia, movement disorder), per investigators judgment
• Genetic epilepsy diagnosis, pathogenic or likely pathogenic variant(s) with consistent phenotype and inheritance pattern
• Weight adequate to complete required study laboratory testing without exceeding maximum allowable blood draws per draw or in a 30 day period per BCH policy

Exclusion Criteria:

• Epileptic spams prior to enrollment
• Tuberous sclerosis complex, trisomy 21 (based on differential response to ES treatment)
• Metabolic diagnosis with targeted treatment (including specific indication for ketogenic diet such as glucose transporter disorder, vitamin dependent epilepsies, and others) or exclusion for the ketogenic diet
• Ongoing treatment with vigabatrin, ACTH, corticosteroids, topiramate or zonisamide. Other anti-seizure medications are permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ketogenic diet; KetoVie® 4:1 Formula will be administered by oral feeding or gastrostomy tube as indicated. The duration of the diet will be from the time of enrollment up to 12 months of age or until 3 months after a diagnosis of Epileptic Spasms (range 3-15 months).

Drug: Ketogenic diet; The ketogenic diet formula will be KetoVie®, supplied by Ajinomoto Cambrooke. Ketogenic diet ratio will aim to achieve ketosis, with a minimum level of beta-hydroxybutyrate of 1.0mmol/L. Ratios of ketogenic diet generally range from 1:1 to 4:1. Ratio will increase per standard clinical care for ketogenic diet initiation. For the trial we will aim to reach a maximum of 4:1 by the 6 week follow-up visit, but stopping at a lower ratio if BHB is ≥ 5mmol/L, CO2 ≤ 18 mmol/L, for tolerance, or to meet protein needs. A minimum 1:1 ratio is required to continue in the trial. Ratios higher than 1:1 are often required to obtain ketosis of ideally 2-5mmol/L in infants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of ketosis	Proportion of subjects assigned to ketogenic diet who achieve ketosis by 6 weeks and maintain a minimum ratio of 1:1 through 3 months after onset of epileptic spasms (ES) or 12 months of age	rom ketogenic diet initiation until 3 months after the diagnosis of ES (if it occurs) or until 12 months of age
EEG compliance	Proportion of subjects who complete EEGs every 6 weeks (+/- 2 weeks) until onset of ES or 12 months of age	From ketogenic diet initiation until the onset of ES (if it occurs) or until 12 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epileptic Spasms Outcome	Proportion of subjects who develop ES by 12 months of age	From ketogenic diet initiation until 12 months of age
EEG Outcome	Proportion of enrolled subjects for whom a study EEG identified ES or identified hypsarrhythmia with subsequent workup leading to diagnosis of ES prior to clinical suspicion	From ketogenic diet initiation until 12 months of age
Safety Outcome	To assess safety of ketogenic diet treatment in infants with genetic DEEs by monitoring the rate of serious adverse events and adverse events, expected and unexpected	From ketogenic diet initiation until the diet is weaned (up to 18 months of age)

Collaborators and Investigators

• Sponsor: Heather Olson
• Collaborators: Boston Children's Hospital Translational Research Program (TRP) Pappendick Family Therapeutic Acceleration Award

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: epilepsy; genetic; prevention; Phase 1; infant; seizures; open label; developmental and epileptic encephalopathy; infantile spasms; epileptic spasms; eeg; Ketogenic diet; epileptic encephalopathy; refractory epilepsy; Epileptic spasms prevention; dietary treatments
• Additional Relevant MeSH Terms: Epileptic Syndromes; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Drug Resistant Epilepsy; Epilepsy; Seizures; Spasms, Infantile; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Diet, Carbohydrate-Restricted; Diet, Ketogenic
• Other Study ID Numbers: P00047586

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