Ketogenic Diet in Pediatric Intractable Epilepsy

Epilepsy in Children Clinical Trial

Official title:

The Efficacy of Ketogenic Diet in Treating Pediatric Intractable Epilepsy and Its Relationship With Changes in Inflammatory Markers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06310954
• Other study ID #: 2022-KY-012
• Status: Recruiting
• Phase: N/A
• Start date: August 11, 2022
• Est. completion date: April 30, 2024

Study information

• Verified date: March 2024
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: DongFang Li
• Phone: +8615509888556
• Email: Tangdx6[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the efficacy of a ketogenic diet in treating pediatric intractable epilepsy and to explore its relationship with changes in inflammatory markers. The investigators plan to recruit 59 participants with intractable epilepsy, 39 of whom will receive a combination of ketogenic diet and conventional antiepileptic drugs, while 20 will receive only conventional drugs. The study will assess the impact of the ketogenic diet on epilepsy control and inflammatory markers, hoping to discover new treatment strategies.

Description:

Evaluation index

1. Safety: Adverse events related to the ketogenic diet

2. Efficacy evaluation:

A. Primary efficacy indicators: brain electrical load index, epilepsy control response rate, inflammatory factor 34 (blood, cerebrospinal fluid) Secondary efficacy indicators: epilepsy seizure-free rate B. Inspection indicators: blood ketone, blood sugar, blood biochemistry testing, etc.; C. Use high-throughput methods to detect absolute counts of cerebrospinal fluid, serum inflammatory factors, and whole blood lymphocyte subpopulations before and after adding a ketogenic diet.

Observation indicators

1. Measurement of ketone body levels Monitor blood ketones (beta-hydroxybutyrate) and blood ketones. Recording time: Record three times a day during the baseline period; record the average blood ketone value at each subsequent follow-up observation.

2. Frequency of epileptic seizures The frequency of epileptic seizures was recorded daily during the start-up period.

3. Efficacy evaluation:

Main efficacy indicators: epilepsy control response rate, seizure-free rate, inflammatory factor levels Epilepsy control response rate: defined as an absolute reduction of ≥50% in seizure frequency at follow-up compared with baseline

=(No attack + Marked effect + Effective)/Total number of cases × 100%. Evaluation of seizure control: No seizures: seizures are completely relieved after treatment; Markedly effective: the number of seizures is reduced by ≥75% after treatment; Effective: the number of seizures is reduced by ≥50% after treatment; Ineffective: the number of seizures is reduced by <50% after treatment.

Seizure-free rate: Seizures were completely controlled at follow-up. = No attack cases/Total number of cases × 100%

4. Safety evaluation Record various adverse events; biochemical monitoring (glucose and lipid metabolism and related tests); other tests: necessary tests according to the condition (blood gas analysis, B-ultrasound, etc.);

5. Physical development Monitor and record height and weight, and conduct physical development evaluation.

6. Cognitive-behavioral development assessment The baseline period, KD weeks 4, 12, and KD week 16 (at the end of the efficacy observation period) were evaluated and recorded using the Gesell score scale.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 59
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 12 Years

Eligibility

Inclusion Criteria:

• Children aged 6 months to 12 years with a diagnosis of intractable epilepsy

• more than four seizures per month

• no metabolic diseases

• no severe liver or kidney dysfunction.

Exclusion Criteria:

• Fat metabolism or other metabolic diseases

• febrile or infectious periods

• contraindications to the ketogenic diet

• children suitable for surgery or parents refusing drug and diet intervention.

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy
• Epilepsy in Children
• Epilepsy Intractable

Intervention

Dietary Supplement:
• Early ketogenic diet combined with conventional pharmacotherapy.
This arm of the trial explores the efficacy of an early initiation of the ketogenic diet in conjunction with conventional antiepileptic drugs (AEDs) for children with refractory epilepsy. The intervention aims to evaluate the impact on seizure frequency, and inflammatory markers, and identify patient characteristics predicting a better response to the ketogenic diet, to improve overall therapeutic response rates in refractory epilepsy.

Drug:
• Common diet combined with conventional pharmacotherapy
Participants in this arm will receive a standard diet without any ketogenic restrictions, alongside conventional antiepileptic drugs. This comparator aims to assess the standard care's efficacy against the experimental intervention, focusing on seizure control, and inflammatory markers, and identifying patient characteristics associated with treatment responsiveness.We know that drug information for registering clinical information is necessary, but our research design is to add ketogenic diets as a supplementary treatment plan when traditional drug treatment is ineffective. Therefore, in terms of specific drug selection, this is not absolutely the same. Depending on individual differences, the choice of drugs will also vary. Control the number of episodes, time, etc., and everyone uses different drugs. Therefore, we cannot decide on a single drug for comparison like traditional content.

Locations

Country	Name	City	State
China	Sun Yat Sen Memorial Hospital, Sun Yat Sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (5)

Chen Z, Brodie MJ, Liew D, Kwan P. Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol. 2018 Mar 1;75(3):279-286. doi: 10.1001/jamaneurol.2017.3949. Erratum In: JAMA Neurol. 2018 Mar 1;75(3):384. — View Citation

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshe SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x. Epub 2009 Nov 3. Erratum In: Epilepsia. 2010 Sep;51(9):1922. — View Citation

Loscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539. — View Citation

Vezzani A, Maroso M, Balosso S, Sanchez MA, Bartfai T. IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun. 2011 Oct;25(7):1281-9. doi: 10.1016/j.bbi.2011.03.018. Epub 2011 Apr 5. — View Citation

Wirrell E, Farrell K, Whiting S. The epileptic encephalopathies of infancy and childhood. Can J Neurol Sci. 2005 Nov;32(4):409-18. doi: 10.1017/s0317167100004388. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epilepsy Control Response Rate	Epilepsy control response rate: defined as an absolute reduction of =50% in seizure frequency at follow-up compared with baseline; =(No attack + Marked effect + Effective)/Total number of cases × 100%.	During the study period (16 weeks)
Secondary	Inflammatory Marker Levels	This indicator aims to evaluate the effect of the ketogenic diet on the levels of inflammatory markers in the blood of children with refractory epilepsy to reveal the potential relationship between the effects of the ketogenic diet and inflammation levels.	During the study period (16 weeks)]