Ketogenic Diet vs Medication for Childhood Absence Epilepsy

Overseen By Eric H Kossoff, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Johns Hopkins University

Must not be taking: Anticonvulsants

Disqualifiers: Glut1 deficiency, Metabolic disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 3 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a modified Atkins diet (high fat, low carb) serves as an effective first treatment for children with new-onset childhood absence epilepsy, instead of starting with medication. Researchers seek to discover if the diet can effectively reduce seizures in these children. Children who experience daily absence seizures and have not yet tried any anticonvulsant drugs may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment option.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have previously used anticonvulsant drugs. It seems the trial is for children who have not yet started medication for epilepsy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Modified Atkins Diet (MAD) is generally safe and effective for treating epilepsy in children. One study found that this diet can greatly reduce seizures. Although close monitoring of the diet is important, serious side effects rarely occur. Most children follow the diet without major issues.

In contrast, common medications for childhood absence epilepsy, such as ethosuximide, valproate, or lamotrigine, are also considered safe but can cause side effects like nausea, tiredness, or dizziness. Consulting a doctor is essential to find the best option. ^{1 2 3 4}

Why are researchers excited about this trial's treatments?

Researchers are excited about using the Modified Atkins Diet for childhood absence epilepsy because it offers a unique dietary approach as opposed to traditional drug therapies like ethosuximide, valproate, or lamotrigine. This diet is high in fat and low in carbohydrates, which can help in managing seizures by altering the body's metabolism to produce ketones. Unlike medication, which can have various side effects, this diet provides a natural alternative that involves close monitoring and support from a dietitian, potentially leading to fewer side effects and a more holistic management of epilepsy.

What evidence suggests that the Modified Atkins Diet could be an effective treatment for childhood absence epilepsy?

Research has shown that the Modified Atkins Diet, tested in this trial, can help reduce seizures in children with epilepsy. Studies have found that this diet can significantly lower seizure frequency, with some children experiencing up to a 40% reduction in just four weeks. Additionally, a review of several studies found that many children on the Modified Atkins Diet had their seizures reduced by more than half. The diet increases certain chemicals in the body called ketones, which seem to help control seizures. This evidence suggests that the diet might be a promising option for managing childhood absence epilepsy. Meanwhile, another arm of this trial involves drug therapy, where families receive the usual care for absence epilepsy, typically involving medications like ethosuximide, valproate, or lamotrigine. ^{2 3 4 5 6}

Who Is on the Research Team?

Eric H Kossoff, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for children aged 3-12 with new-onset childhood absence epilepsy, who experience daily seizures and have specific EEG patterns. They should be generally healthy or have mild disabilities. Kids who've tried a ketogenic diet, taken seizure meds before, or have certain metabolic disorders can't join.

Inclusion Criteria

My child had absence seizures start between ages 3-12.

You have average or slightly impaired intellectual abilities.

I experience daily absence seizures.

Exclusion Criteria

You are not able to follow a high fat, low carbohydrate diet.

You have had seizures in the past, except for febrile seizures.

You have a metabolic disorder that would prevent you from following a special diet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the modified Atkins diet or standard drug therapy for 3 months

3 months

Visits at baseline, 1 month, and 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

EEG and lab assessments at 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Modified Atkins Diet

Trial Overview The study is testing if a modified Atkins Diet (high fat, low carb) can help manage seizures in kids with new-onset absence epilepsy compared to those whose parents choose standard seizure medications instead.

How Is the Trial Designed?

Group I: Diet therapy Experimental Treatment 1 Intervention

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.

Group II: Drug therapy Active Control 1 Intervention

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

Modified Atkins Diet is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Modified Atkins Diet for:

• Refractory epilepsy
• Childhood absence epilepsy
• Glut1 deficiency syndrome
• Infantile spasms

Approved in European Union as Modified Atkins Diet for:

• Refractory epilepsy
• Childhood absence epilepsy
• Glut1 deficiency syndrome
• Infantile spasms

Approved in Canada as Modified Atkins Diet for:

• Refractory epilepsy
• Childhood absence epilepsy
• Glut1 deficiency syndrome
• Infantile spasms

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

The Atkins diet, which is less restrictive than the traditional ketogenic diet, was tested on six patients with intractable epilepsy, showing that five of them maintained a state of ketosis for 6 weeks to 24 months.

Three patients experienced a reduction in seizures and were able to lower their antiepileptic medications, suggesting that the Atkins diet may be a promising alternative therapy for those with epilepsy that does not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the Atkins diet as therapy for intractable epilepsy. Kossoff, EH., Krauss, GL., McGrogan, JR., et al.[2022]

The modified Atkins diet (MAD) was tested in a prospective study involving five children aged 4-18 years with Sturge-Weber syndrome, showing promising results in managing intractable seizures over a 6-month period.

All participants achieved urinary ketosis and experienced improvements in seizure frequency, with three children reporting more than a 50% reduction in seizures, suggesting that MAD may be a safer alternative to the ketogenic diet for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of the modified Atkins diet for Sturge-Weber syndrome. Kossoff, EH., Borsage, JL., Comi, AM.[2010]

In a study of 87 children on the modified Atkins diet for epilepsy, 55% of those who continued for over 6 months experienced more than a 50% improvement in seizures, and 35% became seizure-free after an average of 19.9 months.

The diet showed similar efficacy to short-term studies and long-term ketogenic diets, but side effects included increased lipid levels and gastrointestinal issues, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of children treated with the modified Atkins diet. Chen, W., Kossoff, EH.[2017]

In a review of 17 studies, about 69% of 133 patients with absence epilepsy experienced over a 50% reduction in seizures after following a ketogenic diet, with 34% becoming completely seizure-free.

At Johns Hopkins Hospital, both the ketogenic and modified Atkins diets showed promising results, with 82% of patients achieving over a 50% seizure reduction, and 19% becoming seizure-free, indicating these dietary therapies can be effective for managing idiopathic generalized epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do patients with absence epilepsy respond to ketogenic diets? Groomes, LB., Pyzik, PL., Turner, Z., et al.[2017]

In a study involving four adult patients with drug-resistant epilepsy, the modified Atkins diet led to a significant average reduction of 35% in serum concentrations of antiepileptic drugs (AEDs) after 12 weeks, indicating a potential pharmacokinetic interaction.

This reduction in AED levels could have clinical implications for patients, suggesting that careful monitoring of AED serum concentrations is necessary when implementing the modified Atkins diet as an add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Kverneland, M., Taubøll, E., Selmer, KK., et al.[2018]

A meta-analysis of 12 studies involving 270 adults with intractable epilepsy found that the classical ketogenic diet had a higher efficacy rate of 52%, compared to 34% for the modified Atkins diet, suggesting it may be more effective for seizure control.

Despite its higher efficacy, the classical ketogenic diet had a lower compliance rate of 38%, indicating that adults may find it harder to stick to compared to the modified Atkins diet, which had a compliance rate of 56%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a meta-analysis. Ye, F., Li, XJ., Jiang, WL., et al.[2022]

The modified Atkins diet, used since 2003 for treating refractory epilepsy, has shown similar effectiveness to the traditional ketogenic diet while being more tolerable for patients, with around 400 patients reported across over 30 studies.

This diet can be initiated in a clinical setting without the need for fasting or hospitalization, making it a more accessible option for both children and adults with intractable seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A decade of the modified Atkins diet (2003–2013): Results, insights, and future directions. Kossoff, EH., Cervenka, MC., Henry, BJ., et al.[2019]

In a study of 30 adults with intractable epilepsy, the modified Atkins diet led to a significant reduction in seizures, with 47% of participants experiencing over a 50% reduction in seizures after 1 and 3 months.

The diet was associated with a mean weight loss of 6.8 kg, and those who lost weight showed better seizure control, although some participants experienced side effects like increased cholesterol and a high discontinuation rate of 30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective study of the modified Atkins diet for intractable epilepsy in adults. Kossoff, EH., Rowley, H., Sinha, SR., et al.[2022]

A clinical trial involving 40 children with intractable epilepsy found that both the classic ketogenic diet and the modified Atkins diet resulted in similar efficacy, with over 50% reduction in seizures observed in both groups at various time points.

Specifically, the response rates for the ketogenic diet were 55%, 30%, and 70% at the end of the first, second, and third months, while the Atkins diet showed 50%, 65%, and 70% at the same intervals, indicating that both diets are effective options for managing seizures in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic and atkins diets effect on intractable epilepsy: a comparison. Ghazavi, A., Tonekaboni, SH., Karimzadeh, P., et al.[2021]

In a clinical trial involving 51 children aged 1 to 16 with intractable epilepsy, the modified Atkins diet led to a significant reduction in seizure frequency, with 67% of participants experiencing over a 50% decrease after three months.

The Atkins diet was found to be a safe and well-tolerated alternative therapy, with only rare complications reported, suggesting it could be a viable option for managing refractory childhood epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the Atkins diet as therapy for intractable epilepsy in children. Tonekaboni, SH., Mostaghimi, P., Mirmiran, P., et al.[2022]

The modified Atkins diet, a less restrictive version of the ketogenic diet, has shown good efficacy and tolerability in treating refractory epilepsy, making it a promising dietary intervention.

This diet can be initiated on an outpatient basis without fasting, allowing unlimited protein and fat intake, which may improve adherence compared to more restrictive diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The modified atkins diet in refractory epilepsy. Sharma, S., Jain, P.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11390222/

The Effectiveness of Modified Atkins Ketogenic Diet on ... The MAD reduces the mean seizure frequency in children with intractable epilepsy in the first, third, and sixth months, with a statistical significance in the ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405457722004673

Meta-analysis Modified Atkins diet versus ketogenic diet in ... The primary outcome was the proportion of children who had seizure frequency reduction (SFR) > 50%. The secondary outcomes were SFR >90%, seizure freedom, and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04274179?term=ethosuximide&checkSpell=&rank=10

Ketogenic Diet for New-Onset Absence Epilepsy 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 ...

4. jamanetwork.com jamanetwork.com/journals/jamapediatrics/fullarticle/2769074

Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low ... Seizure reduction with the MAD was also rapid, with an approximate 40% decrease in the number of seizures by 4 weeks; seizure frequency ...

5. epilepsy.com epilepsy.com/treatment/dietary-therapies/modified-atkins-diet

Modified Atkins Diet | Dietary Therapies They had noticed that ketones still remained high and seizures stayed under control. It was first formally studied in children and adults who ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10065201/

Safety, Efficacy, and Tolerability of Modified Atkins Diet in ... A meta-analysis showed that the combined efficacy rates for freedom from seizures, reduction of seizures by 50% or more, and reduction of ...