Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy - Full Text View

Sponsor:	Rikshospitalet HF
Information provided by:	Rikshospitalet HF
ClinicalTrials.gov Identifier:	NCT00552526

Purpose

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.

Condition	Intervention	Phase
Epilepsy Mental Retardation	Dietary Supplement: Ketogenic diet Drug: Antiepileptic drug (AED)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Comparing Ketogenic Diet With the Most Appropriate Antiepileptic Drug- a Randomized Study of Children With Mental Retardation and Drug Resistant Epilepsy

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Diets Epilepsy Seizures

U.S. FDA Resources

Further study details as provided by Rikshospitalet HF:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]
Comparing side effects between the two groups [ Time Frame: Four months ] [ Designated as safety issue: Yes ]
Comparing change in slow activity and epileptic activity by template matching on 24 hour EEG [ Time Frame: Four months ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	November 2007
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Ketogenic diet: Active Comparator	Dietary Supplement: Ketogenic diet Ketogenic diet is a very strict high fat diet
AED: Active Comparator 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.

Arms

Assigned Interventions

Ketogenic diet: Active Comparator

Dietary Supplement: Ketogenic diet

Ketogenic diet is a very strict high fat diet

AED: Active Comparator

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.

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

Eligibility

Ages Eligible for Study:	2 Years to 15 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00552526

Locations

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

Sponsors and Collaborators

Rikshospitalet HF

Investigators

Principal Investigator:

Bjorn Bjurulf, MD

SSE, Nevrological dep., Rikshospitalet University Hospital

More Information

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.

Kossoff EH, McGrogan JR. Worldwide use of the ketogenic diet. Epilepsia. 2005 Feb;46(2):280-9.

Levy R, Cooper P. Ketogenic diet for epilepsy. Cochrane Database Syst Rev. 2003;(3):CD001903. Review.

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.

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.

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. Review.

Responsible Party:	Rikshospitalet-Radiumhospitalet HF ( Rikshospitalet-Radiumhospitalet HF (Bjorn Bjurulf) )
Study ID Numbers:	Ketogenic diet, EudraCT:2006-001776-20
Study First Received:	October 31, 2007
Last Updated:	March 18, 2009
ClinicalTrials.gov Identifier:	NCT00552526 History of Changes
Health Authority:	Norway: Norwegian Medicines Agency; Norway: The National Committees for Research Ethics in Norway

Keywords provided by Rikshospitalet HF:

Epilepsy
Children
Mental retardation
Ketogenic diet
Diet

Additional relevant MeSH terms:

Nervous System Diseases
Central Nervous System Diseases
Brain Diseases
Pharmacologic Actions
Mental Retardation
Signs and Symptoms
Epilepsy

Mental Disorders
Therapeutic Uses
Mental Disorders Diagnosed in Childhood
Neurologic Manifestations
Neurobehavioral Manifestations
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on February 08, 2010