Ketogenic Diet in Infants With Epilepsy (KIWE)

NCT02205931 | Unknown Phase 4 DMC

• 1 other identifier: 13/0656
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 11

Brief Summary

Epilepsy, a condition where individuals are prone to recurrent epileptic seizures, is the most common chronic neurological disorder in children. Epilepsy onset is most common in the first two years of life and is associated with poor prognosis for seizure control and neurodevelopmental outcome. The ketogenic diet (KD) is a medically supervised diet that is high in fat and restricted in carbohydrates and protein. KD therapy has shown to be an effective treatment for seizures in children with epilepsy older than two. Associated benefits include: a reduced requirement for routine and emergency antiepileptic drugs (AED) and fewer seizure related hospital admissions. Although reports suggest that KD therapy improves seizures in younger children there is no high quality trial data that demonstrates effectiveness and safety in this age group. The KD is resource intensive, requiring dietetic and physician time; data is required to justify expansion of services to cater for the apparent need. The investigators therefore propose a prospective multicentre randomised trial to investigate the effectiveness and safety of the KD in children with epilepsy under the age of 2, who have failed to respond to two or more AEDs. Children will be randomly assigned to either receive the KD or further AEDs. The allocated treatment will be started after a 2week baseline period, and it's effectiveness assessed after 8 weeks. Seizure diaries will be used to record seizures and related events, a questionnaire will be used to assess diet tolerance; also growth and blood biochemistry will be monitored. The information obtained from this study is necessary to optimise choices in epilepsy treatment, aiming to improve outcomes and thus determine whether and when the KD should should be used.

Conditions

Epilepsy

Keywords

Epilepsy; Ketogenic diet; Antiepileptic drugs; Randomised controlled trial

Outcome Measures

Primary Outcomes (1)

• Number of seizures

  Number of seizures experienced during weeks 6 - 8

  6 - 8 weeks

Secondary Outcomes (1)

• Responder rate

  8 weeks

Other Outcomes (1)

• Retention on treatment

  12 months

Study Arms (2)

Ketogenic diet

EXPERIMENTAL

8 week trial of the ketogenic diet (KD) therapy. Children allocated to KD therapy will have their diets individually calculated by a paediatric dietitian with consideration of daily calorie requirements, adequate protein intake for growth and vitamin and mineral supplementation. All diets will be implemented according to a classical KD protocol, i.e. based on a ratio of fat to carbohydrate and protein that will usually be between 2:1 and 4:1.

Other: Ketogenic diet

Antiepileptic drug therapy

ACTIVE COMPARATOR

The control intervention will be drug therapy with the most appropriate further antiepileptic drug (AED) for a particular child, depending on their presenting seizures and syndrome and previous drugs used, and chosen by the expert clinician responsible for management of the patient's epilepsy according to a standardised manual (consensus document) written following the initial workshop of the paediatric neurologists from all the trial centres.

Drug: Antiepileptic drug therapy

Interventions

Ketogenic diet OTHER

The ketogenic diet is a high fat diet designed to mimic the effects on the body of starvation. The premise is the main energy intake is fat, which is utilised in the body and produces ketones.

Ketogenic diet

Antiepileptic drug therapy DRUG

The control intervention will be drug therapy with the most appropriate further antiepileptic drug for a particular child, depending on their presenting seizures and syndrome and previous drugs used, and chosen by the expert clinician responsible for management of the patient's epilepsy.

Also known as: Carbamazepine, Clobazam, Clonazepam, Ethosuximide, Lacosmide, Lamotrigine, Levetiracetam, Nitrazepam, Phenytoin, Rufinamide, Sodium Valproate, Stiripentol, Topiramate, Vigabatrin, Zonisamide

Antiepileptic drug therapy

Eligibility Criteria

• Age: 1 Month - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 1 month and 24 months of age (not beyond second birthday at baseline).
• Diagnosis of epilepsy confirmed.
• At least an average of 4 seizures/week in baseline period.
• Failed response to previous trial of two anti-epileptic drugs. In the case of infantile spasms this could include a trial of corticosteroids.
• Children with written informed consent from parent/guardian.

You may not qualify if:

• Age \<1m or \> 24 months of age
• No secure diagnosis of epilepsy
• \< 4 seizures/week on average in baseline period
• Trial of \< 2 AEDs
• Continues on corticosteroids in previous 3 months prior to randomisation
• Metabolic disease contraindicating use of the ketogenic diet e.g. pyruvate carboxylase deficiency, MCAD from previous medical investigation and screening at baseline.
• Progressive neurological disease
• Severe gastroesophageal reflux
• Previous treatment with the ketogenic diet
• Concurrent participation in another clinical trial of an investigational medicinal product.
• Patients who are prescribed AEDs not listed in the trial IMPs

Sponsors & Collaborators

• University College, London: lead
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Alder Hey Children's NHS Foundation Trust: collaborator
• Bristol Royal Hospital for Children: collaborator
• Birmingham Women's and Children's NHS Foundation Trust: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• Manchester University NHS Foundation Trust: collaborator
• Sheffield Children's NHS Foundation Trust: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• Lancashire Care NHS Foundation Trust: collaborator
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator
• St George's University Hospitals NHS Foundation Trust: collaborator

Study Sites (11)

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

RECRUITING

Bristol Royal Hospital for Children

Bristol, BS2 8AE, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Lancashire Teaching Hospitals NHS Foundation Trust

Lancashire, United Kingdom

RECRUITING

Leeds Teaching Hospital

Leeds, LS1 3EX, United Kingdom

RECRUITING

Alder Hey Children's Hospital

Liverpool, L12 2AP, United Kingdom

RECRUITING

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

RECRUITING

St George's University Hospitals NHS Foundation Trust

London, United Kingdom

RECRUITING

Royal Manchester Children's Hospital

Manchester, M13 0JE, United Kingdom

RECRUITING

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

RECRUITING

Sheffield Children's NHS Foundation Trust

Sheffield, United Kingdom

RECRUITING

Related Publications (1)

• Titre-Johnson S, Schoeler N, Eltze C, Williams R, Vezyroglou K, McCullagh H, Freemantle N, Heales S, Kneen R, Marston L, Martland T, Nazareth I, Neal E, Lux A, Parker A, Agrawal S, Fallon P, Cross JH. Ketogenic diet in the treatment of epilepsy in children under the age of 2 years: study protocol for a randomised controlled trial. Trials. 2017 Apr 26;18(1):195. doi: 10.1186/s13063-017-1918-3.

  PMID: 28446244 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

Diet, Ketogenic; Carbamazepine; Clobazam; Clonazepam; Ethosuximide; Lamotrigine; Levetiracetam; Nitrazepam; Phenytoin; rufinamide; Valproic Acid; stiripentol; Topiramate; Vigabatrin; Zonisamide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Benzodiazepinones; Succinimides; Imides; Organic Chemicals; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Triazines; Acetamides; Amides; Acetates; Acids, Acyclic; Carboxylic Acids; Hydantoins; Imidazolidines; Imidazoles; Azoles; Pentanoic Acids; Valerates; Fatty Acids, Volatile; Fatty Acids; Lipids; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Amino Acids; Amino Acids, Peptides, and Proteins; Sulfonamides; Sulfones; Sulfur Compounds; Isoxazoles

Study Officials

• Helen Cross, FRCP(UK)

  UCL Institute of Child Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helen Cross, FRCP(UK)

CONTACT

0044 207 599 4105; h.cross@ucl.ac.uk

Siobhan Titre-Johnson, MSc

CONTACT

s.titre-johnson@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: August 1, 2014
• Study Start: January 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2019
• Last Updated: May 4, 2017

Record last verified: 2017-05

Locations

GB (11)