Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy

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 Overview

• Status: Unknown
• Conditions: Epilepsy; Mental Retardation
• Intervention / Treatment: Dietary supplement: Ketogenic diet; Drug: Antiepileptic drug (AED)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • SSE, Nevrological dep. , Rikshospitalet University hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketogenic diet	Dietary supplement: Ketogenic diet; Ketogenic diet is a very strict high fat diet
Active Comparator: AED; Most appropriate antiepileptic drug	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparing amount of patients with 100%, >90% and >50% reduction in number of seizures between the two groups of seizures	4 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparing the parents´evaluation of change in quality of life and cognitive function between the two groups. The parents will answer a questionary.	Four months
Comparing side effects between the two groups	Four months
Comparing change in slow activity and epileptic activity by template matching on 24 hour EEG	Four months
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	13 months
Is the effect of the ketogenic diet as good in children with severe mental retardation as in children with less severe learning disabilities?	4 and 12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Bjorn Bjurulf, MD, SSE, Nevrological dep., Rikshospitalet University Hospital

Publications and helpful links

General Publications

• Pulsifer MB, Gordon JM, Brandt J, Vining EP, Freeman JM. Effects of ketogenic diet on development and behavior: preliminary report of a prospective study. Dev Med Child Neurol. 2001 May;43(5):301-6. doi: 10.1017/s0012162201000573.
• Hallböök T Effects of vagus nerve stimulation and ketogenic diet on quality of life and changes in EEG and sleep Lund University 2006
• Kossoff EH, McGrogan JR. Worldwide use of the ketogenic diet. Epilepsia. 2005 Feb;46(2):280-9. doi: 10.1111/j.0013-9580.2005.42704.x.
• Levy R, Cooper P. Ketogenic diet for epilepsy. Cochrane Database Syst Rev. 2003;(3):CD001903. doi: 10.1002/14651858.CD001903.
• Kang HC, Kim YJ, Kim DW, Kim HD. Efficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicentric experience. Epilepsia. 2005 Feb;46(2):272-9. doi: 10.1111/j.0013-9580.2005.48504.x.
• Kossoff EH, Pyzik PL, McGrogan JR, Vining EP, Freeman JM. Efficacy of the ketogenic diet for infantile spasms. Pediatrics. 2002 May;109(5):780-3. doi: 10.1542/peds.109.5.780.
• Lefevre F, Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: A systematic review of efficacy. Pediatrics. 2000 Apr;105(4):E46. doi: 10.1542/peds.105.4.e46.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Anticipated): January 1, 2011
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: October 31, 2007
• First Submitted That Met QC Criteria: November 1, 2007
• First Posted (Estimate): November 2, 2007

Study Record Updates

• Last Update Posted (Estimate): March 19, 2009
• Last Update Submitted That Met QC Criteria: March 18, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: Epilepsy; Children; Diet; Ketogenic diet; Mental retardation
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Epilepsy; Intellectual Disability; Drug Resistant Epilepsy; Anticonvulsants
• Other Study ID Numbers: Ketogenic Diet; EudraCT:2006-001776-20