Official Title: “Comparing Ketogenic Diet With the Most Appropriate Antiepileptic Drug- a Randomized Study of Children With Mental Retardation and Drug Resistant Epilepsy”

This is an open randomized controlled study in children with mental retardation and refractory epilepsy in which treatment with ketogenic diet (KD) is compared with treatment with the antiepileptic drug (AED), not tried by the patient before, which we consider to be the most appropriate AED for the patient.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study

Study Primary Completion Date: January 2011

There are two trials in the study: - To compare the effect of the ketogenic diet with the effect of the most appropriate AED after 4 months - To evaluate the effect of the ketogenic diet after 4 and 13 months on the children who have been randomized to this treatment, the seizure frequency is compared with the frequency before start of treatment

Intervention(s) in this Clinical Trial

• Dietary Supplement: Ketogenic diet
  • Ketogenic diet is a very strict high fat diet
• Drug: Antiepileptic drug (AED)
  • An AED,not used by the patient before, which we consider to be the most appropriate will be given orally or by gastrostomy. Serum concentration, the body weight, side effects and effects on the epilepsy will be considered when deciding the dose of the AED. Traditions for amount of medicine/kg body weight or optimal serum concentration at our center will be followed. This tradition will be the same as in other major European epilepsy centers but might propose lower, but not higher amounts than recommended by the drug company. Drugs from ACT groups N03A, N05BA, N05CD, H02A or S01EC will be used including prednisolon,levetiracetam, valproate, carbamazepine, oxcarbazepine, topiramate, felbamate, zonisamide, vigabatrin, tiagabil, lamotrigine, pregabalin, rufinamide, clobazam, clonazepam, tiagabine, gabapentin, phenytoin, phenobarbital, ethosuximide, acetazolamide, nitrazepam and other new antiepileptic drugs that might be released during the study period.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Ketogenic diet
• Active Comparator: AED
  • Most appropriate antiepileptic drug

Primary Measures

• Comparing amount of patients with 100%, >90% and >50% reduction in number of seizures between the two groups of seizures
  • Time Frame: 4 months
    Safety Issue?: No

Secondary Measures

• Comparing the parents´evaluation of change in quality of life and cognitive function between the two groups. The parents will answer a questionary.
  • Time Frame: Four months
    Safety Issue?: No
• Comparing side effects between the two groups
  • Time Frame: Four months
    Safety Issue?: Yes
• Comparing change in slow activity and epileptic activity by template matching on 24 hour EEG
  • Time Frame: Four months
    Safety Issue?: No
• Investigating side effects and change in number of seizures, change in EEG, quality of life and cognitive function after 13 months of treatment with the ketogenic diet
  • Time Frame: 13 months
    Safety Issue?: Yes
• Is the effect of the ketogenic diet as good in children with severe mental retardation as in children with less severe learning disabilities?
  • Time Frame: 4 and 12 months
    Safety Issue?: No

Inclusion Criteria:

• The patient is mentally retarded
• The patient has tried at least 3 different AED:s including one combination with two or more different AED:s.
• The parents are willing to include their child in the study after written and verbal information.
• Patients with all types of epilepsy can be included.
• The patient has at least 6 seizures/month.
• The patient is submitted to our epilepsy center.
• The seizures are possible to count
• The patient has either generalized epilepsy, multifocal epilepsy or an epilepsy where it is undetermined whether it is localized or generalized such as Dravet syndrome classified as G40.3-G40.9 in ICD X.

Exclusion Criteria:

• The family is expected to have compliance problems with treatment and/or seizure registration.
• The hospital which have submitted the patient is not willing to accept the inpatient stays and the procedures that are necessary for the project.
• The patient`s seizures are under acceptable control.
• The patient has got a vagus nerve stimulator implanted within the last 18 months, has started a new antiepileptic drug within the last 2 months or has changed his antiepileptic drugs the last month.
• The patient has a medical condition, for example a metabolic disease, where ketogenic diet is contraindicated.
• The patient has a localized epilepsy classified as G40.0-G40.2 in ICD X.
• The patient`s nutritional status is not good enough or intake of fluid is to small to permit treatment with ketogenic diet.
• The patient has within the last 2 months been using medications or herbal medications that has a considerable effect on glucose metabolism, such as oral glucocorticoids.
• The patient has within the last 2 months been using medications or herbal medications that has a considerable effect on metabolism of AED:s.
• The patient uses herbal medicine which can interact with AED or Ketogenic diet.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Rikshospitalet-Radiumhospitalet HF

Overall Clinical Trial Officials and Contacts

Bjorn Bjurulf, Cand med Principal Investigator SSE, Nevrological dep., Rikshospitalet University Hospital  

Overall Contact: Bjorn Bjurulf, cand. med 47 67501000 bjorn.bjurulf@epilepsy.no

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00552526

Study ID Number: Ketogenic diet

ClinicalTrials.gov Identifier: NCT00552526

Health Authority: Norway: Norwegian Medicines Agency