Impact of Ketogenic Diet on Lipoproteins in Refractory Epilepsy

Study Overview
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Brief Summary
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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.

Detailed Description
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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: a. 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. n. Determine the concentration of antioxidants in plasma: α-tocopherol, beta-carotene and retinol. O. 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. Q. Determine the concentration of hepatic enzymes R. Determine the leptin, adiponectin, ghrelin and resistin S. To evaluate the liver ultrasound and carotid ultrasound

Official Title
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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

Conditions
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Epilepsy, Cardiovascular Disease, Non-alcoholic Fatty Liver Disease, Quality of Life

Intervention / Treatment
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* Dietary Supplement: ketogenic diet


Participation Criteria
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Eligibility Criteria
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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 .

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group control<br>classical ketogenic diet | Dietary Supplement: ketogenic diet<br>* Ketogenic diet with high fat (90%)<br>|
| Active Comparator: Group case<br>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<br>* Ketogenic diet with high fat (90%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Socioeconomic and clinical profile | age, income, disease, parent´s education, use of drugs and supplements, type of seizures, questions about quality of life | average of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index | BMI according growth charts | average of 3 months | 
| Fat mass | Fat mass by impedance bioeletrical | average of 3 months | 
| Fat free mass | fat free mass by impedance bioeletrical | average of 3 months | 
| Phase angle | phase angle mass by impedance bioeletrical | average of 3 months |