Ketogenic Therapy for Epilepsy

Overseen By Peggy R. Borum, Ph.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must be taking: Ketogenic diet

Disqualifiers: Inability to metabolize diet, non-compliance

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

400 Participants Needed

Trial Summary

What is the purpose of this trial?

Approximately a fourth of children with seizures do not respond adequately to available therapy. Ketogenic therapy has a long history as treatment for intractable epilepsy, but there is no agreement concerning how it works and what is the best way to administer it. This natural history study will collect data pertaining to both questions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Ketogenic Therapy for Epilepsy?

Research shows that dietary therapies like the ketogenic diet, medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment can significantly reduce seizures in about 30-60% of children with epilepsy after 6 months of treatment. These diets have been proven effective, especially for those who do not respond to traditional medications. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

The ketogenic diet, used for treating epilepsy, is generally safe but can have side effects like nausea, vomiting, diarrhea, constipation, and weight loss. It requires strict adherence and monitoring, and not everyone may be able to commit to it. ^{1 2 6 7 8}

How is ketogenic therapy different from other treatments for epilepsy?

Ketogenic therapy is unique because it uses a high-fat, low-carbohydrate diet to manage epilepsy, offering an alternative to traditional medications. It includes various diet forms like the classic ketogenic diet, modified Atkins diet, and low glycemic index treatment, which are less restrictive and can be tailored to individual needs, making it a flexible option for those with drug-resistant epilepsy. ^{1 3 4 5 9}

Research Team

Peggy R. Borum, Ph.D.

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for children with seizures not well-managed by current treatments. Participants must be prescribed a ketogenic diet by their doctor, able to process high fat and low carbohydrate diets according to lab tests, and willing to follow the therapy regimen and maintain records.

Inclusion Criteria

You are following a diet called the ketogenic diet as prescribed by your doctor.

You have lab tests showing that your body can process a diet high in fat and low in carbohydrates.

Patients that can be compliant with administration of the therapy and with record keeping

Exclusion Criteria

Your lab tests show that your body cannot process a diet high in fat and low in carbohydrates.

Patients at risk of being non-compliant with administration of the therapy and with record keeping

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ketogenic Therapy, which involves an altered macronutrient intake to induce ketosis and reduce seizures

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of dyslipidemia and growth

4-8 weeks

Treatment Details

Interventions

• Ketogenic Therapy

Trial Overview The study investigates how Ketogenic Therapy affects children with epilepsy. It aims to understand how this high-fat, low-carbohydrate diet works as a treatment and determine the most effective way of administering it.

Participant Groups

Group I: Ketogenic Therapy Experimental Treatment 1 Intervention

Ketogenic Therapy will be administered.

Ketogenic Therapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ketogenic Diet for:

• Intractable epilepsy
• Refractory epilepsy
• Seizure control

Approved in United States as Ketogenic Diet for:

• Intractable epilepsy
• Refractory epilepsy
• Seizure control

Approved in Canada as Ketogenic Diet for:

• Intractable epilepsy
• Refractory epilepsy
• Seizure control

Approved in Japan as Ketogenic Diet for:

• Intractable epilepsy
• Refractory epilepsy
• Seizure control

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Findings from Research

The ketogenic diet (KD) has been effectively used since 1921 to treat severe epilepsy, and recent evidence suggests that alternative, less restrictive versions like the Medium Chain Triglyceride (MCT) KD, modified Atkins diet (MAD), and low glycaemic index treatment (LGIT) are nearly as effective as the classical KD.

While the alternative diets show promising efficacy, there is currently no randomized controlled trial (RCT) data for MAD and LGIT, indicating that patient-specific factors such as age, epilepsy type, and lifestyle should guide the choice of diet for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative diets to the classical ketogenic diet--can we be more liberal? Miranda, MJ., Turner, Z., Magrath, G.[2022]

Ketogenic diets, including various forms like the classic ketogenic diet and modified Atkins diet, can lead to a significant reduction in seizures for 30-60% of children after 6 months of treatment, making them an effective option for managing epilepsy.

Despite their efficacy, these dietary therapies come with potential side effects and require strict adherence, which may not be feasible for all families, highlighting the need for careful consideration and support from healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary treatments for epilepsy: management guidelines for the general practitioner. Lee, PR., Kossoff, EH.[2011]

The ketogenic diet (KD) and its variations, including the medium-chain triglyceride ketogenic diet and modified Atkins diet, have been shown to significantly reduce seizures in patients with medically refractory epilepsy.

Early initiation of dietary treatments for epilepsy is recommended, as they can be effective alternatives to traditional medications, rather than being considered only as last-resort options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dietary treatment of medically refractory epilepsy in children and adolescents]. Høgsbro-Rode, F., Johannesen, KMH., Stubbings, V., et al.[2018]

Dietary therapies, including the ketogenic diet and others, have been shown to be effective in improving seizure control for children with intractable epilepsy who do not respond to anticonvulsant medications.

These dietary approaches are recommended to be considered earlier in treatment due to their proven efficacy, tolerability, and cost-effectiveness, offering an alternative to traditional medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic treatments for intractable epilepsy. Kelley, SA., Hartman, AL.[2017]

Dietary therapies, such as the ketogenic diet, are gaining recognition as effective treatments for epilepsy, especially for patients who do not respond to traditional medications, with new indications emerging for conditions like Dravet syndrome and infantile spasms.

Recent research has highlighted the potential neuroprotective effects of these diets, suggesting they may not only help control seizures but also offer benefits for other neurological conditions, including Alzheimer's disease and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets: new advances for metabolism-based therapies. Kossoff, EH., Hartman, AL.[2022]

The ketogenic diet (KD) is considered a relatively safe treatment for refractory childhood epilepsy, with severe adverse effects occurring in less than 0.5% of children, and no deaths attributed to the diet.

Common adverse effects include gastrointestinal disturbances and hyperlipidemia, but the main reason for discontinuation of the diet was lack of efficacy rather than safety concerns, highlighting the need for careful medical supervision during its implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. Cai, QY., Zhou, ZJ., Luo, R., et al.[2018]

The ketogenic diet (KD) is an effective nonpharmacologic treatment for intractable childhood epilepsy, but there is a need for standardized protocols for its administration, as practices vary globally.

A consensus statement created by a panel of 26 experts provides comprehensive recommendations on patient evaluation, diet implementation, monitoring, and discontinuation of the KD, emphasizing the importance of best evidence in clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus statement on clinical implementation of the ketogenic diet: agreement, flexibility, and controversy. Kossoff, EH.[2017]

In a pilot study involving 12 adults with refractory epilepsy, the ketogenic diet (KD) led to a significant reduction in seizure frequency, with a 38.4% decrease in the first 4 months and a 44.1% decrease over the entire treatment period.

The diet was generally safe, with only mild adverse effects reported, and 56% of participants experienced a significant reduction in seizures, indicating that KD can be an effective adjunctive treatment for adults with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet treatment in adults with refractory epilepsy. Klein, P., Janousek, J., Barber, A., et al.[2017]

The ketogenic diet (KD) and modified Atkins diet (MAD) have shown significant efficacy in reducing seizure frequency in children and adolescents with refractory epilepsy, with 35-56.1% of participants achieving a reduction of 50% or more in seizures compared to only 6-18.2% in control groups.

Gastrointestinal side effects were the most common adverse effects reported, but no severe adverse effects were noted, suggesting that these dietary interventions are generally safe for young patients with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis. Sourbron, J., Klinkenberg, S., van Kuijk, SMJ., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Alternative diets to the classical ketogenic diet--can we be more liberal? [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Dietary treatments for epilepsy: management guidelines for the general practitioner. [2011]

3. Denmark pubmed.ncbi.nlm.nih.gov

[Dietary treatment of medically refractory epilepsy in children and adolescents]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Metabolic treatments for intractable epilepsy. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Ketogenic diets: new advances for metabolism-based therapies. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

International consensus statement on clinical implementation of the ketogenic diet: agreement, flexibility, and controversy. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Ketogenic diet treatment in adults with refractory epilepsy. [2017]

9. Germany pubmed.ncbi.nlm.nih.gov

Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis. [2021]