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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a ketogenic diet (high-fat, low-carbohydrate) can help children with epilepsy whose seizures don't improve with standard treatments. Researchers aim to understand how this diet works and the best way to use it. Children who might be suitable for this trial are those already prescribed the ketogenic diet by their doctor and who can handle a high-fat, low-carb diet without issues. Participants must follow the diet and track their progress. As an unphased trial, this study offers a unique opportunity for children to potentially benefit from a specialized diet while contributing to valuable research.

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 prior data suggests that ketogenic therapy is safe for treating epilepsy?

Research shows that a ketogenic diet, high in fats and low in carbohydrates, is generally well-tolerated by people with epilepsy. Studies indicate that this diet can be a safe option for treating epilepsy that doesn't respond to medication. Reviews have found that both the classic ketogenic diet and its variations, like the modified Atkins diet, are safe for many patients. However, some people might experience side effects such as constipation or high cholesterol.

Including medium-chain triglycerides (MCTs) in the diet also maintains a good safety record. MCTs are special fats that can enhance the diet's effectiveness. While the diet may not work for everyone, it has been used since the 1970s and is considered safe for many who try it. Overall, ketogenic therapy has a strong history of safety in managing seizures. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional epilepsy treatments, which often involve medications to control seizures, ketogenic therapy is a high-fat, low-carbohydrate diet that alters the body's energy source from glucose to ketones. This unique mechanism of action can lead to fewer seizures for some individuals, particularly those who do not respond well to standard anti-seizure medications. Researchers are excited about ketogenic therapy because it offers a non-pharmacological option that might reduce side effects associated with long-term medication use, providing a potentially effective alternative for managing epilepsy.

What is the effectiveness track record for ketogenic therapy in treating epilepsy?

Research has shown that the ketogenic diet, high in fats and low in carbohydrates, can help control seizures in some people with epilepsy. Studies have found this diet particularly useful for those who do not respond well to standard treatments. Evidence from both animal and human studies supports the diet's ability to reduce seizure frequency and severity. The medium-chain triglyceride (MCT) version of the diet, which uses specific types of fats, allows for more carbohydrates while still managing seizures effectively. Overall, the ketogenic diet has a long history of success in treating difficult-to-control epilepsy, especially in children. ^{2 3 6 7 8}

Who Is on the Research Team?

Peggy R. Borum, Ph.D.

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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) 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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923003732

Ketogenic Diets: Evidence for Short- and Long-term Efficacy This review discusses the animal and human evidence for both short- and long-term benefits of dietary therapies.

2. epilepsy.com epilepsy.com/treatment/dietary-therapies/ketogenic-diet

Ketogenic Diet for Seizures The "classic" ketogenic diet is a special high-fat, low-carbohydrate diet that helps to control seizures in some people with epilepsy.

3. nature.com nature.com/articles/s41392-021-00831-w

Ketogenic diet for human diseases: the underlying ... The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4002181/

Ketogenic Diets: New Advances for Metabolism-Based ... The medium-chain triglyceride (MCT) diet has been used since the 1970s, using more of this highly ketogenic oil in order to free up more carbohydrates. The MCT ...

5. univmed.org univmed.org/ejurnal/index.php/medicina/article/view/1749

Effectiveness of medium-chain triglyceride diet and low ... Modified Atkins diet versus low glycemic index treatment for drug-resistant epilepsy in children: an open label, randomized controlled trial.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40290041/

Clinical Efficacy and Safety of the Ketogenic Diet in ... In this narrative review, we examine the clinical efficacy and safety of the classic ketogenic diet (cKD) and its variants, including the modified Atkins diet ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666149724000124

Ketogenic diet in clinical practices This meta-analysis aims to consolidate the evidence regarding the impact of ketogenic diets on patients with epilepsy in clinical practice.

8. aepi.biomedcentral.com aepi.biomedcentral.com/articles/10.1186/s42494-024-00150-x

Efficacy and safety of modified medium-chain triglyceride ... The modified MCTKD with MCTs providing 20–30% of energy has a good safety in patients with drug-resistant epilepsy, but its effectiveness needs to be enhanced.