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NCT Number: NCT04274179

Ketogenic Diet for New-Onset Absence Epilepsy

The ketogenic diet is a medical therapy for epilepsy that is used nearly predominantly for refractory epilepsy (after 2-3 drugs have been tried and failed). However, there is both published evidence for first-line use (infantile spasms, Glut1 deficiency syndrome) and also anecdotal experience (families choosing to change the child's (or the family' own) diet rather than use anticonvulsant medications). Childhood absence epilepsy (refractory) has been published as being responsive to ketogenic diet therapy by the investigators' group previously. This is a small, prospective, 3 month trial to assess if using a modified Atkins diet is a feasible and effective option for new-onset childhood absence epilepsy. The investigators will compare to a group of children in which the parents have declined and chose to start anticonvulsant medications.

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Key information

Age range

3 year–12 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location status: Recruiting

Location contact

Ania Dabrowski, MD

SUB_INVESTIGATOR

Courtney Haney, RD

SUB_INVESTIGATOR

Danielle DeCampo, MD

SUB_INVESTIGATOR

Eric H Kossoff, MD

CONTACT

[email protected]

410-955-9100

Eric H Kossoff, MD

PRINCIPAL_INVESTIGATOR

Eva Catenaccio, MD

SUB_INVESTIGATOR

Lindsay Schleifer, MD

SUB_INVESTIGATOR

Rachel Penn, MD

SUB_INVESTIGATOR

Zahava Turner, RD

SUB_INVESTIGATOR

About this study

The ketogenic diet has been in continuous use since 1921 for children and adult with medically-refractory epilepsy. One of the major unanswered questions is whether it would be as effective for children with new-onset epilepsy. Although logically, this would be the case, it remains to be shown in clinical trials. Additionally, it is much easier to take a medication than to change dietary habits and there is doubt whether families would truly wish to try dietary therapy first (or stay on dietary therapy if not effective for a 6 month trial period).

There is limited published evidence supporting the use of the ketogenic diet as a first-line therapy for infantile spasms, myoclonic astatic epilepsy, and in some situations where a family member had success and the family wishes to start it first. However, these are relatively rare conditions. The emergence of the modified Atkins diet as an outpatient, quickly-initiated, non-fasting approach since 2003 has changed the concept of dietary therapy towards a much less restrictive, potentially emergent therapy. In this way, using dietary therapy could potentially be started before medications for a willing family.

The use of dietary therapy (including the modified Atkins diet) for childhood absence epilepsy goes back decades, but was recently profiled in a review article from the investigators' group. In this publication, 17 studies were identified, and 69% of 133 children with refractory childhood absence epilepsy had a >50% seizure reduction and 34% were seizure-free. At the investigators' center, 21 children as of 2011 had been treated with dietary therapy with 19% seizure-freedom. The question of whether results would be similar (or better) for children with new-onset absence epilepsy was unanswered.

The standard treatments for childhood absence epilepsy (ethosuximide, valproate, lamotrigine) are effective in ~50% of children by 16-20 weeks. However, side effects exist and include stomach upset, inattention, mood disturbance, rash, liver function test abnormalities, and fatigue. Families at times do ask about avoiding treatment completely, especially as this epilepsy usually resolves in puberty and convulsions only occur in 20% (most children have brief staring spells only). In addition, families do also ask about "nonpharmacologic" treatment, but to date the investigators have not recommended it due to lack of data.

This study will have 20 children in each arm (diet and drug) with ability to crossover. Parents with a child with new-onset absence epilepsy will choose between the two therapies. Visits will be at baseline, 1 month and 3 months. EEG, labs and clinic visits will be paid by the parent's insurance (not free).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Children ages 3-12 years at seizure onset with classic childhood absence epilepsy clinically.
  • Normal intellect or mild disability
  • EEG with confirmed 3/second spike-wave discharges, usually with hyperventilation
  • Daily reported absence seizures.
  • Generalized convulsions allowed

Exclusion criteria

  • Previous treatment with any anticonvulsant drug
  • Previous use of a ketogenic dietary therapy for epilepsy or any other condition
  • Glut1 deficiency syndrome
  • Metabolic disorder known that would preclude dietary therapy
  • Dietary restrictions for which a high fat, low carbohydrate diet would be precluded.
  • Prior history of epilepsy (febrile seizures allowed)
  • Unwilling to consent to study procedures or return for visits

Treatment and study plan

Modified Atkins diet

Other

Low carb (20g/day), high fat, moderate protein diet. Started as an outpatient in clinic.

Absence epilepsy medications

Drug

At neurologist's discretion. *OF NOTE< THIS ARM IS COMPLETED

Other names: Ethosuximide, valproate or lamotrigine

Primary outcomes

  1. Change in seizure frequency

    Time frame: At 1 and 3 months post treatment

    Parental report of seizure frequency.

Secondary outcomes

  1. Tolerability of diet therapy as assessed by restrictiveness of the diet therapy

    Time frame: At 3 months

    Diet therapy restrictiveness will be assessed with an open ended questionnaire that asks "how hard has it been for the child?". Completely subjective with no scale or scoring.

  2. Tolerability of diet therapy as assessed by restrictiveness of the diet therapy

    Time frame: At 6 months

    Diet therapy restrictiveness will be assessed with an open ended questionnaire that asks "how hard has it been for the child?". Completely subjective with no scale or scoring.

  3. Duration of diet therapy

    Time frame: Up to 3 months post treatment

    Duration of diet therapy in months.

  4. Tolerability of diet therapy as assessed by change in urinary ketones

    Time frame: At 1 and 3 months post treatment

    Urinary ketones in mg/dl will be measured (80-160mg/dl is considered large ketosis).

  5. EEG changes (normalization of the baseline spike-wave bursts)

    Time frame: Baseline and at 3 months post treatment

    30 minute routine EEG including hyperventilation to induce seizures, compare 3 months to baseline

Study contacts

Contact information is provided by the study sponsor or research team.

Eric H Kossoff, MD

CONTACT

[email protected]

4109559100

Sponsors and collaborators

Lead sponsor

Johns Hopkins University

Other

Registry information

Official study title

A Prospective, Case-control Evaluation of Ketogenic Dietary Therapy for New-onset Childhood Absence Epilepsy

Important dates

Study start
2020
Primary completion
2028
Study completion
2028
First posted
Feb 18, 2020
Registry last updated
May 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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