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Ketogenic Diet for New-Onset Absence Epilepsy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04274179
Recruitment Status : Not yet recruiting
First Posted : February 18, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Absence Epilepsy Ketogenic Dieting Epilepsy, Absence Other: Modified Atkins Diet Drug: Absence epilepsy medications Phase 3

Detailed Description:

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two arms (diet and drugs) with ability to cross-over at 1 or 3 months.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Case-control Evaluation of Ketogenic Dietary Therapy for New-onset Childhood Absence Epilepsy
Estimated Study Start Date : August 1, 2020
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : May 1, 2023


Arm Intervention/treatment
Experimental: Diet therapy
Modified Atkins Diet - high fat, low carbohydrate, outpatient initiated approach. Parents will check urine ketones twice weekly and follow by email, phone and clinic. Labs at baseline and 3 months. Dietitian support.
Other: Modified Atkins Diet
Low carb (20g/day), high fat, moderate protein diet. Started as an outpatient in clinic.

Active Comparator: Drug therapy
Families will have the usual care for absence epilepsy at the discretion of the family's neurologist and the family choice. Typically ethosuximide bis in die (BID), however, if convulsions have occurred or other factors are involved, the child may be started on valproate or lamotrigine. The child will continue medications with dose adjustment and antiseizure drug levels checked as usual.
Drug: Absence epilepsy medications
At neurologist's discretion
Other Name: Ethosuximide, valproate or lamotrigine




Primary Outcome Measures :
  1. Change in seizure frequency [ Time Frame: At 1 and 3 months post treatment ]
    Parental report of seizure frequency.


Secondary Outcome Measures :
  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



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Ages Eligible for Study:   3 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04274179


Contacts
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Contact: Eric H Kossoff, MD 4109559100 ekossoff@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Contact: Eric H Kossoff, MD    410-955-9100    ekossoff@jhmi.edu   
Principal Investigator: Eric H Kossoff, MD         
Sub-Investigator: Zahava Turner, RD         
Sub-Investigator: Courtney Haney, RD         
Sub-Investigator: Eva Catenaccio, MD         
Sub-Investigator: Danielle DeCampo, MD         
Sub-Investigator: Rachel Penn, MD         
Sub-Investigator: Ania Dabrowski, MD         
Sub-Investigator: Lindsay Schleifer, MD         
Sponsors and Collaborators
Johns Hopkins University
Investigators
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Principal Investigator: Eric H Kossoff, MD Johns Hopkins University
Publications:
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04274179    
Other Study ID Numbers: IRB00241856
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johns Hopkins University:
ketogenic
diet
absence
Additional relevant MeSH terms:
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Epilepsy
Epilepsy, Absence
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epilepsy, Generalized
Epileptic Syndromes
Lamotrigine
Valproic Acid
Ethosuximide
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Sodium Channel Blockers
Enzyme Inhibitors
GABA Agents
Neurotransmitter Agents
Antimanic Agents