Absence EpilepsyPhase 3NCT04274179
Ketogenic Diet for New-Onset Absence Epilepsy
A Phase 3 study testing Modified Atkins Diet and Absence epilepsy medications in people with Absence Epilepsy and Ketogenic Dieting, run by Johns Hopkins University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 12 years
- Conditions the study is for
- Absence Epilepsy, Ketogenic Dieting, Epilepsy, Absence
- What is being tested?
- Modified Atkins Diet and Absence epilepsy medications
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2020to 1 May 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Eric H Kossoff, MD, 410-955-9100, ekossoff@jhmi.edu
Eric H Kossoff, MD
About this study
Official title: A Prospective, Case-control Evaluation of Ketogenic Dietary Therapy for New-onset Childhood 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.
Read the 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).
- Conditions
- Absence Epilepsy, Ketogenic Dieting, Epilepsy, Absence
- Being tested
- Modified Atkins Diet, Absence epilepsy medications
- Keywords
- ketogenic, diet, absence
- Medical subject headings
- Epilepsy, Absence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Atkins DietOther
Low carb (20g/day), high fat, moderate protein diet. Started as an outpatient in clinic.
Absence epilepsy medicationsDrug
Also called Ethosuximide, valproate or lamotrigine
At neurologist's discretion. *OF NOTE< THIS ARM IS COMPLETED
| Study group | Role | What they receive |
|---|---|---|
| Diet therapy | Experimental | 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. Receives: Other: Modified Atkins Diet |
| Drug therapy | Active comparator | 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. **OF NOTE, THIS ARM IS COMPLETED Receives: Drug: Absence epilepsy medications |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in seizure frequency
Parental report of seizure frequency.
Measured: At 1 and 3 months post treatment
Secondary outcomes (5)
Tolerability of diet therapy as assessed by restrictiveness of the diet therapy
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.
Measured: At 3 months
Tolerability of diet therapy as assessed by restrictiveness of the diet therapy
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.
Measured: At 6 months
Duration of diet therapy
Duration of diet therapy in months.
Measured: Up to 3 months post treatment
Tolerability of diet therapy as assessed by change in urinary ketones
Urinary ketones in mg/dl will be measured (80-160mg/dl is considered large ketosis).
Measured: At 1 and 3 months post treatment
EEG changes (normalization of the baseline spike-wave bursts)
30 minute routine EEG including hyperventilation to induce seizures, compare 3 months to baseline
Measured: Baseline and at 3 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2020
- Study start10 Aug 2020
- Primary completion1 May 2028 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Absence EpilepsyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Two arms (diet and drugs) with ability to cross-over at 1 or 3 months.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric H Kossoff, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04274179
- Sponsor's protocol ID
- IRB00241856
- Status last verified
- May 2026
- First submitted
- 14 Feb 2020
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Groomes LB, Pyzik PL, Turner Z, Dorward JL, Goode VH, Kossoff EH. Do patients with absence epilepsy respond to ketogenic diets? J Child Neurol. 2011 Feb;26(2):160-5. doi: 10.1177/0883073810376443. Epub 2010 Jul 20.
PubMed 20647578Kossoff EH, Hedderick EF, Turner Z, Freeman JM. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia. 2008 Sep;49(9):1504-9. doi: 10.1111/j.1528-1167.2008.01606.x. Epub 2008 Apr 10.
PubMed 18410363
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Case-control Evaluation of Ketogenic Dietary Therapy for New-onset Childhood Absence Epilepsy
- ClinicalTrials.gov ID
- NCT04274179
- Acronym / sponsor ID
- IRB00241856
- Conditions
- Absence Epilepsy, Ketogenic Dieting, Epilepsy, Absence
- Keywords
- ketogenic, diet, absence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 10 Aug 2020 (actual)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 18 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two arms (diet and drugs) with ability to cross-over at 1 or 3 months.
| Arm | Type | Receives |
|---|---|---|
| Diet therapy | Experimental | Other: Modified Atkins DietModified 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. |
| Drug therapy | Active comparator | Drug: Absence epilepsy medicationsFamilies 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. **OF NOTE, THIS ARM IS COMPLETED |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified Atkins DietLow carb (20g/day), high fat, moderate protein diet. Started as an outpatient in clinic. | Other | Diet therapy |
| Absence epilepsy medicationsAlso: Ethosuximide, valproate or lamotrigineAt neurologist's discretion. *OF NOTE< THIS ARM IS COMPLETED | Drug | Drug therapy |
Primary outcome
Change in seizure frequency
Time frame: At 1 and 3 months post treatment
Parental report of seizure frequency.
5 secondary outcomes
Tolerability of diet therapy as assessed by restrictiveness of the diet therapy
Time frame: At 3 months
Tolerability of diet therapy as assessed by restrictiveness of the diet therapy
Time frame: At 6 months
Duration of diet therapy
Time frame: Up to 3 months post treatment
Tolerability of diet therapy as assessed by change in urinary ketones
Time frame: At 1 and 3 months post treatment
EEG changes (normalization of the baseline spike-wave bursts)
Time frame: Baseline and at 3 months post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Background: PubMed 20647578Groomes LB, Pyzik PL, Turner Z, Dorward JL, Goode VH, Kossoff EH. Do patients with absence epilepsy respond to ketogenic diets? J Child Neurol. 2011 Feb;26(2):160-5. doi: 10.1177/0883073810376443. Epub 2010 Jul 20.
- Background: PubMed 18410363Kossoff EH, Hedderick EF, Turner Z, Freeman JM. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia. 2008 Sep;49(9):1504-9. doi: 10.1111/j.1528-1167.2008.01606.x. Epub 2008 Apr 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eric H Kossoff, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Modified Atkins Diet and Absence epilepsy medications in people with Absence Epilepsy and Ketogenic Dieting, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eric H Kossoff, MD (4109559100, ekossoff@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in seizure frequency (time frame: At 1 and 3 months post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04274179, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.