Efficacy of Low Glycemic Index Diet Versus Classic Ketogenic Diet in Pediatric Epilepsy Treatment

Mashhad University of Medical Sciences

Status: Enrolling

Conditions: Seizure; Drug Resistant Epilepsy; Epilepsy

Treatments: Other: Low Glycemic index therapy; Other: Classic Ketogenic Diet

Study type: Interventional

Funder types: Other

Identifiers

NCT06703983

4030150

Details and patient eligibility

About

Epilepsy is a common disease among children. Today, treating epilepsy remains a major challenge, with many children affected by this condition. According to reports, 30% of children with epilepsy do not respond well to treatment. Various methods are available for managing epilepsy, one of the most accepted therapies for this condition are dietary therapies. Numerous studies have shown that dietary therapy is an effective and can have reasonable response in treating seizure.

The most commonly used dietary intervention is the Classic Ketogenic Diet (CKD). In the CKD, approximately 90% of calories come from fat, making it a highly restrictive regimen that causes significant challenges for children to follow. Many studies have reported low adherence rates due to its difficulty, with a substantial number of patients discontinuing the diet over time.

Some studies have explored the use of the Low Glycemic Index Therapy(LGIT), another form of the ketogenic diet, in managing drug-resistant epilepsy can be successful. In the LGIT, 60% of energy is derived from fat, 30% from protein, and 10% from carbohydrates. Due to the reduced fat content and greater dietary flexibility, this diet has fewer side effects and is easier to follow. Studies have also shown higher adherence rates to LGIT compared to CKD.

Although limited research is available on LGIT, existing studies suggest that it may be as effective as CKD in treating epilepsy. Given the widespread prevalence and severe complications associated with untreated epilepsy in children, Further research into dietary therapies is crucial, as untreated epilepsy can lead to irreversible damage in children.

The aim of this study is to compare the effectiveness of the Low Glycemic Index therapy and the Classic Ketogenic Diet in epilepsy treatment. If LGIT proves to be as successful as CKD, it could be considered a suitable alternative for managing epilepsy.

In this randomized clinical trial, 40 children with drug-resistant epilepsy will be enrolled. Participants will be selected from patients referred by Pediatric Neurologists to dietitians for ketogenic diet therapy.

After obtaining informed consent, participants will be randomly assigned using a block randomization method to one of two groups: the LGIT group or the CKD group. At the end of three months, the two groups will be compared in terms of seizure frequency and duration using statistical tests. The effectiveness of LGIT relative to CKD will be reported.

Full description

Epilepsy is a widespread neurological conditions in children. Recent estimates suggest that 1 in 418 children live with active epilepsy. Epilepsy can negatively impact a child's growth, learning, and development, leading to cognitive impairments, learning disabilities, developmental issues, and, in severe cases, death. Therefore, finding an effective treatment is necessary. Although many drugs have been developed for the treatment of epilepsy, one-third of patients still have drug-resistant epilepsy (DRE) that does not respond well to available epilepsy drugs.

According to the International League Against Epilepsy (ILAE), drug-resistant epilepsy(DRE) is defined as a condition in which, despite the use of at least two appropriate antiepileptic drugs at the correct dose, the epilepsy still persists and the patient continues to experience seizures.According to this definition, 30% of children with epilepsy suffer from DRE. DRE patients respond poorly to pharmacologic therapies and they need alternative therapies such as surgery, vagus nerve stimulation, and dietary therapy.

In 2018, an expert consensus committee suggested the ketogenic diet as a treatment for children with DRE based on the current scientific knowledge.In epilepsy dietary therapy, Ketogenic diet can be used. The ketogenic diet is an effective, non-invasive, and non-pharmacologic treatment for refractory childhood epilepsy. The ketogenic diet for epilepsy treatment has been used since the 1920s and in different articles. It had few to no neurotoxic effects compared to multiple anti-seizure medicines.

The ketogenic diet consists of four forms: Classic ketogenic diet, Low glycemic index therapy(LGIT), Modified Atkins diet(MAD), and MCT Ketogenic diet. According to clinical guideline of the National Institute for Health and Clinical Excellence (NICE), Ketogenic diet is a non-pharmacologic treatment for children with DRE. while the exact mechanism is still unclear, it has shown to be effective.

The classic Ketogenic diet (CKD) is usually described by the ratio of fat to carbs and protein. Mostly, a 4:1 CKD is prescribed but there are other forms like 3:1 and 2.5:1 CKD.

Although the CKD is effective in the treatment of epilepsy in many studies, most patients discontinue the diet because of its unpalatable and restrictive features specially in longer periods. To increase adherence, newer forms of the KD, such as MAD and MCTKD diet have been developed.

In LGIT, carbohydrate intake is restricted to foods with glycemic index below 50. This diet consists of 60% of calories from fat, 30% from protein, and 10 from carbohydrates.

MAD is another form of Ketogenic diet. MAD consist of 65% calories from fat, 25% of calories from protein and 10% of calories from carbohydrates (17).

In MCTKD diet, 50-70% of total energy intake is from fat, including 20-30% for MCTs and 30-40% for LCTs, with protein contributing 20-30% of calories and carbohydrates providing the remaining 20% of calories. In MCTKD most of MCT oil is derived from octanoic (C8) and decanoic (C10) fatty acids.

Various clinical trials have examined the effectiveness of various forms of ketogenic diet in treating epilepsy. Our review indicates that all studies show effectiveness of ketogenic in reducing seizures, although the degree of effectiveness varied.

This study aims to address some gaps in previous research and find out how much effective LGIT is compared to Classic Ketogenic diet.A total of 40 patients will be enrolled, with 20 participants in the CKD arm and 20 in the LGIT arm.Seizure reduction will be monitored and recorded by the parents.

At the end of the study period, seizure outcomes will be analyzed and categorized into four groups:

Seizure-free participants. Participants with >90% seizure reduction. Participants with >50% seizure reduction. Participants with <50% seizure reduction (non-responders). This study can provide valuable insights for clinicians and researchers.

Enrollment: 40 estimated patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Children between 2 and 18 years old who still have epilepsy despite receiving 2 or more medications

Children with genetic disease need to receive ketogenic diet (pyruvate dehydrogenase deficiency and GLUT-1 transporter deficiency)

Exclusion criteria

Parents' disapproval of the child's participation in the study Having liver and kidney diseases Doctor's disapproval based on the patient's condition Absolute contraindications to the ketogenic diet

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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40 participants in 2 patient groups

Classic Ketogenic diet

Active Comparator group

Description:

This study includes two arms, with participants allocated using a blocked randomization process. In the control arm, participants will follow the Classic Ketogenic Diet (CKD), a standard dietary therapy for epilepsy.The CKD is highly restrictive, with approximately 90% of total calories derived from fat, 6% from protein, and 4% from carbohydrates and this diet is really challenging for patients to follow. This arm will include 20 participants with drug-resistant epilepsy for whom the ketogenic diet has been asked by a pediatric neurologist and prescribed by a registered dietitian.Participants will be followed for three months, with parents documenting seizure frequency at each monthly follow-up visit. At the end of the study period, seizure outcomes will be analyzed and categorized into four groups: Seizure-free participants. Participants with \>90% seizure reduction. Participants with \>50% seizure reduction. Participants with \<50% seizure reduction (non-responders).

Treatment:

Other: Classic Ketogenic Diet

Other: Low Glycemic index therapy

Low glycemic index therapy

Active Comparator group

Description:

In intervention arm, patients will receive a low glycemic index diet(LGIT). The LGIT is a modified form of the ketogenic diet that restricts carbohydrate intake to sources with a glycemic index of less than 50. This diet provides approximately 60% of total calories from fat, 30% from protein, and 10% from carbohydrates.In the LGIT arm, there will be 20 participants who will follow a LGIT diet under the care of a Registered Dietitian and a Pediatric Neurologist. After three months, seizure outcomes will be categorized into the following groups: At the end of the study period, seizure outcomes will be analyzed and categorized into four groups: Seizure-free participants. Participants with \>90% seizure reduction. Participants with \>50% seizure reduction. Participants with \<50% seizure reduction (non-responders). Results will be analyzed and compared with Classic Ketogenic diet which serves as the standard dietary therapy for epilepsy.

Treatment:

Other: Classic Ketogenic Diet

Other: Low Glycemic index therapy