Clinical trial NCT06703983: Efficacy of Low Glycemic Index Diet Versus Classic Ketogenic Diet in Pediatric Epilepsy Treatment
Official title: Comparison of the Effect of Low Glycemic Index Diet Compared to the Classical Ketogenic Diet in Reducing the Number of Seizures in Children With Drug Resistant Epilepsy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Seizure
Epilepsy
Drug Resistant Epilepsy
Keywords: Ketogenic diet
Classic ketogenic diet
Low glycemic index diet
LGIT
CKD
Refractory epilepsy
seizure
Drug resistant epilepsy
Lead sponsor: Mashhad University of Medical Sciences
Sponsor class: OTHER
First posted: 2024-11-25
Enrollment: 40
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is an open-label randomized clinical trial with two arms:

Low Glycemic Index therapy (LGIT) Classic Ketogenic Diet (CKD) Each arm will include 20 participants, allocated using a block randomization process. After three months, seizure reduction outcomes will be compared between the two groups.

All 40 participants in both arms will recieve diet for 3 months.Parents will monitor and report the impact of the dietary therapy on seizure frequency, and each participant will be categorized into one of four groups based on the reported reduction:

1. Seizure free:No more seizures reported
2. More than 90% seizure reduction
3. More than 50% seizure reduction
4. Less than 50% seizure reduction Based on previous studies, a reduction of less than 50% is considered an unsuccessful therapy.

After three months, all 40 participants will be evaluated to determine the effectiveness of each diet in treating epilepsy and results will be analyzed and reported.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Seizure reduction
timeFrame: 3 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Mashhad
country: Iran, Islamic Republic of
facility: Mashhad University of Medical Sciences
state: Razavi Khorasan
Study officials:
References: