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

Official title

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

Overview

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 suspected or confirmed genetic seizure disorders to establish if the protocol of early ketogenic diet administration and ES evaluation is safe and feasible.

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 suspected or confirmed 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 suspected or confirmed 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 suspected or confirmed 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.

Interventions

• 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

Primary outcome measures

• Achievement of ketosis [Time frame: rom ketogenic diet initiation until 3 months after the diagnosis of ES (if it occurs) or until 12 months of age]
• EEG compliance [Time frame: From ketogenic diet initiation until the onset of ES (if it occurs) or until 12 months of age]

Secondary outcome measures (3)

• Epileptic Spasms Outcome [Time frame: From ketogenic diet initiation until 12 months of age]
• EEG Outcome [Time frame: From ketogenic diet initiation until 12 months of age]
• Safety Outcome [Time frame: From ketogenic diet initiation until the diet is weaned (up to 18 months of age)]

Eligibility criteria

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
• Suspected or confirmed genetic diagnosis as a cause for epilepsy
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Boston Children's Hospital — Boston

Identifiers

NCT: NCT06700811 · P00047586

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗