Ketonutri: Impact of Ketogenic Diet on Lipoproteins in Refractory Epilepsy

Sponsor

University of Sao Paulo (Other)

Overall Status

Unknown status

CT.gov ID

NCT02644239

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The ketogenic diet is a non-pharmacological treatment prescribed especially for children and indicated in most specialized centers for patients with refractory epilepsy. The composition of the ketogenic diet is based on high-fat, low-carbohydrate, moderate protein content, and the production of ketone bodies is the probable mechanism involved in the control of seizures. The relationship between the treatment of the ketogenic diet and changes in oxidative characteristics, physical and lipid are not well established. Some studies show a significant increase in total cholesterol and triglycerides in children being treated with ketogenic diet, but other studies have shown that changes in lipid profile in the long term do not appear to be significant, beyond the influence of these changes on coronary heart disease are unknown. The studies performed in the last two decades have shown that besides the changes in the lipid profile, oxidative modification of lipoproteins are essential for the initiation and progression of atherosclerosis and physical properties of lipoproteins also appear to be involved in this process, suggesting that the particle size of lipoproteins, through the analysis of subfractions can provide more details of the cardiovascular risk. Thus, this projetct aims to compare the effects of the classical ketogenic diet with the ketogenic diet modified with lower content of saturated fatty acids and a higher content of monounsaturated and polyunsaturated, the oxidative changes of LDL, lipidomic profile, the concentration of antioxidants in production inflammatory cytokines and the subfractions of LDL and HDL in children and adolescents with refractory epilepsy, the clinical effect on controlling epilepsy.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy Cardiovascular Disease Non-alcoholic Fatty Liver Disease Quality of Life	Dietary Supplement: ketogenic diet	N/A

Detailed Description

Controlled clinical trial composed of children of adolescents aged 1 to 19 years with refractory epilepsy drug polytherapy (antiepileptic drugs). Children of both sexes are being included. The control group receive the diet classical ketogenic while the case group receive the ketogenic diet modified reduction of at least 20% of the supply of saturated fat and increase> 50% of the acid supply monounsaturated fatty, increase> 50% of acid content polyunsaturated fatty and a lower ratio w6 / w3 at least 50% compared to classical diet used by the control group. Patients are followed in 3 times: baseline, 3 months and 6 months after the intervention.

Exclusion criteria: Children and adolescents who use any type of hormone replacement; Children and adolescents who present diagnosis of diabetes mellitus and hypothyroidism or hyperthyroidism; Children and adolescents with acute illnesses such as heart disease and kidney disease that prevent indication of the DC evaluated by medical history and complete physical examination by the neurologist doctor in charge of the clinic.

Outcome Measures:

Characterize the sample as the demographics (gender, age), scioeconomic, quality of life and clinical; B. To assess dietary intake through food records; c. Evaluate the anthropometric profile and classify the nutritional status (Z score of body mass index for age [ZBMI / I]); d. Assess body composition (percentage of fat, lean mass, total body water and phase angle); e. Determine the concentration of cholesterol and triglycerides, lipoproteins (TC, TG, LDL and HDL); f. Determine the concentration of apolipoproteins: APOA-1 and APO-B; g. Detect the concentration of ketone bodies in the plasma (β-hydroxybutyrate); H. Detecting LDL (-) and oxidized LDL in plasma; i. To detect anti-LDL autoantibodies (-) and anti-oxLDL autoantibodies in plasma; j. Determine subfractions HDL, LDL and high LDL particle size; k. To evaluate the concentration of non-esterified fatty acids (NEFAs); l. Assess the concentration of fatty acids in plasma; m. To assess the concentration of substances reactive to thiobarbituric acid (TBARS) in plasma.
Determine the concentration of antioxidants in plasma: α-tocopherol, beta-carotene and retinol.

Determining the lipidomic plasma profile gathering lipid species in more classes associated with the risk of cardiovascular disease; P. Detecting inflammatory markers: Tumor necrosis factor (TNF-α), interleukin (IL-6) in plasma.
Determine the concentration of hepatic enzymes R. Determine the leptin, adiponectin, ghrelin and resistin S. To evaluate the liver ultrasound and carotid ultrasound

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Classic Ketogenic Diet and Modified: Evaluation of the Therapeutic Potential and Impact on the Oxidative Profile, Lipidomic, Inflammatory and Size of Lipoproteins in Children and Adolescents With Refractory Epilepsy

Study Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Jul 1, 2020

Anticipated Study Completion Date :

Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group control classical ketogenic diet	Dietary Supplement: ketogenic diet Ketogenic diet with high fat (90%)
Active Comparator: Group case Group case: modified ketogenic diet to reduce at least 20% saturated fat, up> 50% of the acid supply monounsaturated, increasing> 50% polyunsaturated fatty acid content and a lower ratio w6 / w3 at least 50% compared to classic diet used by the control group	Dietary Supplement: ketogenic diet Ketogenic diet with high fat (90%)

Arm

Intervention/Treatment

Active Comparator: Group control

classical ketogenic diet

Dietary Supplement: ketogenic diet

Ketogenic diet with high fat (90%)

Active Comparator: Group case

Group case: modified ketogenic diet to reduce at least 20% saturated fat, up> 50% of the acid supply monounsaturated, increasing> 50% polyunsaturated fatty acid content and a lower ratio w6 / w3 at least 50% compared to classic diet used by the control group

Dietary Supplement: ketogenic diet

Ketogenic diet with high fat (90%)

Outcome Measures

Primary Outcome Measures

Socioeconomic and clinical profile [average of 3 months]
age, income, disease, parent´s education, use of drugs and supplements, type of seizures, questions about quality of life

Secondary Outcome Measures

Body Mass Index [average of 3 months]
BMI according growth charts
Fat mass [average of 3 months]
Fat mass by impedance bioeletrical
Fat free mass [average of 3 months]
fat free mass by impedance bioeletrical
Phase angle [average of 3 months]
phase angle mass by impedance bioeletrical

Other Outcome Measures

Assessement of food intake [average of 3 months]
Food record applied during 3 days to each time
Ketone bodies [average of 3 months]
Concentration of B-hydroxybutirate in plasma. Determination with kit Ranbut (Randox Laboratories Limited, Reino Unido).
Lipid profile [average of 3 months]
Total cholesterol, LDL, HDL, TG
NEFAS [average of 3 months]
Concentration in plasma. Determination with kit NEFAS(Randox Laboratories Limited, Reino Unido)
LDL oxidized [average of 3 months]
Determination in plasma
Antioxidant [average of 3 months]
Determination of antioxidant concentration in plasma by HPLC
Metabolomic (lipidomic) [average of 3 months]
Determination in plasma by mass spectrometry
Subfractions of Lipoproteins [average of 3 months]
Determination in plasma by Lipoprint
Liver enzymes [average of 3 months]
Concentration of AST, ALT, GGT
Hepatic function [average of 3 months]
Ultrasound liver
Leptin [average of 3 months]
Determination in plasma
Resistin [average of 3 months]
Determination in plasma

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 19 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria: Participate in the study children and adolescents of both sexes with age 1-19 years diagnosed with refractory epilepsy drug polytherapy ( antiepileptic drugs ) and indication of treatment with KD .

Exclusion Criteria: Children and adolescents who use any type of hormonal replacement ;

Children and adolescents who submit diagnosis of diabetes mellitus and hypothyroidism or hyperthyroidism ;
Children and adolescents showing acute disorders as heart disease and kidney diseases .