Impact of Ketogenic Diet on Lipoproteins in Refractory Epilepsy

Quality of Life Clinical Trial

— Ketonutri  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02644239
• Other study ID #: Faculdade de Saúde Pública USP
• Status: Recruiting
• Phase: N/A
• First received: October 13, 2015
• Last updated: December 28, 2015
• Start date: June 2012
• Est. completion date: July 2020

Study information

• Verified date: December 2015
• Source: University of Sao Paulo
• Contact: Nagila Raquel Teixeira Damasceno, Ph D
• Phone: +55(11) 3061-7865
• Email: nagila[@]usp.br
• Is FDA regulated: No
• Health authority: Brazil: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 19 Years

Eligibility

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 .

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Epilepsy
• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Quality of Life

Intervention

Dietary Supplement:
• ketogenic diet
Ketogenic diet with high fat (90%)

Locations

Country	Name	City	State
Brazil	Nagila Raquel Teixeira Damasceno	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (13)

Avogaro P, Bon GB, Cazzolato G. Presence of a modified low density lipoprotein in humans. Arteriosclerosis. 1988 Jan-Feb;8(1):79-87. Erratum in: Arteriosclerosis 1988 Nov-Dec;8(6):857. — View Citation

Avogaro P, Cazzolato G, Bittolo-Bon G. Some questions concerning a small, more electronegative LDL circulating in human plasma. Atherosclerosis. 1991 Nov;91(1-2):163-71. — View Citation

de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007 Sep;85(9):660-7. — View Citation

Faulin Tdo E, de Sena-Evangelista KC, Pacheco DB, Augusto EM, Abdalla DS. Development of immunoassays for anti-electronegative LDL autoantibodies and immune complexes. Clin Chim Acta. 2012 Jan 18;413(1-2):291-7. doi: 10.1016/j.cca.2011.10.004. Epub 2011 Oct 18. — View Citation

Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. Epub 2014 Apr 14. Review. — View Citation

Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J Jr. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005 Apr;46(4):470-2. — View Citation

Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007 Mar;119(3):535-43. Review. — View Citation

Kossoff EH, Zupec-Kania BA, Amark PE, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Helen Cross J, Dahlin MG, Donner EJ, Klepper J, Jehle RS, Kim HD, Christiana Liu YM, Nation J, Nordli DR Jr, Pfeifer HH, Rho JM, Stafstrom CE, Thiele EA, Turner Z, Wirrell EC, Wheless JW, Veggiotti P, Vining EP; Charlie Foundation, Practice Committee of the Child Neurology Society; Practice Committee of the Child Neurology Society; International Ketogenic Diet Study Group. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia. 2009 Feb;50(2):304-17. doi: 10.1111/j.1528-1167.2008.01765.x. Epub 2008 Sep 23. — View Citation

Kwiterovich PO Jr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM. Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA. 2003 Aug 20;290(7):912-20. — View Citation

Lee PR, Kossoff EH. Dietary treatments for epilepsy: management guidelines for the general practitioner. Epilepsy Behav. 2011 Jun;21(2):115-21. doi: 10.1016/j.yebeh.2011.03.008. Epub 2011 Apr 21. Review. — View Citation

Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009 Dec 1;54(23):2129-38. doi: 10.1016/j.jacc.2009.09.009. Review. — View Citation

Liu YM, Williams S, Basualdo-Hammond C, Stephens D, Curtis R. A prospective study: growth and nutritional status of children treated with the ketogenic diet. J Am Diet Assoc. 2003 Jun;103(6):707-12. — View Citation

WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006 Apr;450:76-85. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessement of food intake	Food record applied during 3 days to each time	average of 3 months	Yes
Other	Ketone bodies	Concentration of B-hydroxybutirate in plasma. Determination with kit Ranbut (Randox Laboratories Limited, Reino Unido).	average of 3 months	Yes
Other	Lipid profile	Total cholesterol, LDL, HDL, TG	average of 3 months	Yes
Other	NEFAS	Concentration in plasma. Determination with kit NEFAS(Randox Laboratories Limited, Reino Unido)	average of 3 months	Yes
Other	LDL oxidized	Determination in plasma	average of 3 months	Yes
Other	Antioxidant	Determination of antioxidant concentration in plasma by HPLC	average of 3 months	Yes
Other	Metabolomic (lipidomic)	Determination in plasma by mass spectrometry	average of 3 months	Yes
Other	Subfractions of Lipoproteins	Determination in plasma by Lipoprint	average of 3 months	Yes
Other	Liver enzymes	Concentration of AST, ALT, GGT	average of 3 months	Yes
Other	Hepatic function	Ultrasound liver	average of 3 months	Yes
Other	Leptin	Determination in plasma	average of 3 months	Yes
Other	Resistin	Determination in plasma	average of 3 months	Yes
Primary	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	Yes
Secondary	Body Mass Index	BMI according growth charts	average of 3 months	Yes
Secondary	Fat mass	Fat mass by impedance bioeletrical	average of 3 months	Yes
Secondary	Fat free mass	fat free mass by impedance bioeletrical	average of 3 months	Yes
Secondary	Phase angle	phase angle mass by impedance bioeletrical	average of 3 months	Yes