Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) in Human Obesity

Obesity Clinical Trial

— OBEPALIP  

Official title:

Cellular and Molecular Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) on Adipose Tissue: Potential Application in Human Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01138774
• Other study ID #: OBEPALIP
• Status: Completed
• Phase: N/A
• First received: May 21, 2010
• Last updated: May 27, 2015
• Start date: January 2010
• Est. completion date: December 2012

Study information

• Verified date: February 2012
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to analyze the effects of Lipoic acid and/or EPA supplementation on weight loss, lipid profile, insulin resistance, oxidative and inflammation parameters, metabolomic profile as well as on adipose tissue gene profile in healthy overweight/obese subjects following an energy-restricted diet.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• Women

• Ages between 20 and 45 years, and with regular menstrual cycles

• Body Mass Index (BMI) between 27.5 and 39.9 kg/m2

• Weight unchanged (± 3 kg) for the last 3 months

• All subjects should have an overall physical and psychological condition that the investigator believes is in accordance with the overall aim of the study.

Exclusion Criteria:

• Use of prescription medication

• To suffer from any chronic metabolic or obesity related disease, hepatic or renal systemic disease: Hypertension, dislipidemia, type 1 or 2 diabetes, thyroid function disorders, cirrhosis, fatty liver, etc.

• Food allergies or food intolerance expected to come up during the study

• Special diets (Atkins, vegetarian, etc.) prior three months the start of the study.

• Eating disorders

• Surgically treated obesity

• Pregnant or lactating women or planning to be pregnant in the next two months

• Alcohol or drug abuse (based on clinical parameters)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Body Fat
• Insulin Resistance
• Obesity

Intervention

Dietary Supplement:
• Double blind dietary intervention with EPA and lipoic acid
Placebo-controlled dietary intervention during 10 weeks. All groups will have a dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline, supplemented with eicosapentaenoic acid (EPA) and/or lipoic acid (LA).

Locations

Country	Name	City	State
Spain	Department of Nutrition, Food Science, Physiology and Toxicology. University of Navarra	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

References & Publications (13)

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond). 2009 Aug 14;117(6):243-9. doi: 10.1042/CS20090020. — View Citation

Lorente-Cebrián S, Bustos M, Marti A, Martinez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. Mol Nutr Food Res. 2010 May;54 Suppl 1:S104-11. doi: 10.1002/mnfr.200900522. — View Citation

Marrades MP, Martínez JA, Moreno-Aliaga MJ. Differences in short-term metabolic responses to a lipid load in lean (resistant) vs obese (susceptible) young male subjects with habitual high-fat consumption. Eur J Clin Nutr. 2007 Feb;61(2):166-74. Epub 2006 Aug 9. — View Citation

Marrades MP, Milagro FI, Martínez JA, Moreno-Aliaga MJ. Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers. Biochem Biophys Res Commun. 2006 Jan 20;339(3):785-9. Epub 2005 Nov 22. — View Citation

Navas-Carretero S, Pérez-Granados AM, Schoppen S, Vaquero MP. An oily fish diet increases insulin sensitivity compared to a red meat diet in young iron-deficient women. Br J Nutr. 2009 Aug;102(4):546-53. doi: 10.1017/S0007114509220794. Epub 2009 Feb 12. — View Citation

Parra D, Ramel A, Bandarra N, Kiely M, Martínez JA, Thorsdottir I. A diet rich in long chain omega-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss. Appetite. 2008 Nov;51(3):676-80. doi: 10.1016/j.appet.2008.06.003. Epub 2008 Jun 14. — View Citation

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Baena MJ, Marti A, Martínez JA, Moreno-Aliaga MJ. Differential inflammatory status in rats susceptible or resistant to diet-induced obesity: effects of EPA ethyl ester treatment. Eur J Nutr. 2008 Oct;47(7):380-6. doi: 10.1007/s00394-008-0738-3. Epub 2008 Sep 18. — View Citation

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Marti A, Martínez JA, Moreno-Aliaga MJ. Down-regulation in muscle and liver lipogenic genes: EPA ethyl ester treatment in lean and overweight (high-fat-fed) rats. J Nutr Biochem. 2009 Sep;20(9):705-14. doi: 10.1016/j.jnutbio.2008.06.013. Epub 2008 Sep 30. — View Citation

Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Martínez JA, Moreno-Aliaga MJ. Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats. Br J Nutr. 2009 Apr;101(7):1059-67. doi: 10.1017/S0007114508048307. Epub 2008 Aug 28. — View Citation

Pérez-Matute P, Pérez-Echarri N, Martínez JA, Marti A, Moreno-Aliaga MJ. Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2007 Feb;97(2):389-98. — View Citation

Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Barber A, Martínez JA, Moreno-Aliaga MJ. Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transport. J Physiol Biochem. 2009 Mar;65(1):43-50. — View Citation

Ramel A, Martinéz A, Kiely M, Morais G, Bandarra NM, Thorsdottir I. Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults. Diabetologia. 2008 Jul;51(7):1261-8. doi: 10.1007/s00125-008-1035-7. Epub 2008 May 20. — View Citation

Ramel A, Martinez JA, Kiely M, Bandarra NM, Thorsdottir I. Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction. Nutrition. 2010 Feb;26(2):168-74. doi: 10.1016/j.nut.2009.04.002. Epub 2009 May 31. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight Loss	Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.	Week 0 (baseline)	No
Primary	Weight Loss	Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.	Week 2	No
Primary	Weight Loss	Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.	Week 4	No
Primary	Weight Loss	Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.	week 6	No
Primary	Weight Loss	Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.	Week 8	No
Primary	Weight Loss	Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.	Week 10 (end of treatment)	No
Primary	Body composition and Anthropometric parameters	Changes in body composition will be analyzed by Dual X-ray Absorptiometry (DXA) and by bioimpedance, and hip and waist circumferences will be measured.	Week 0 (Baseline)	No
Primary	Body composition and anthropometric parameters	Changes in body composition will be analyzed by Dual X-ray Absorptiometry (DXA) and by bioimpedance, and hip and waist circumferences will be measured.	Week 10 (end of treatment)	No
Primary	Glucose metabolism parameters	Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index	Week 0 (baseline)	No
Primary	Glucose metabolism parameters	Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index	Week 10 (end of treatment)	No
Primary	Lipid metabolism biomarkers	Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies.	Week 0 (baseline)	No
Primary	Lipid metabolism biomarkers	Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies.	Week 10 (end of treatment)	No
Secondary	Blood Pressure and Cardiovascular Risk biomarkers	Blood pressure, PAI-1 and VEGF will be measured.	Baseline	No
Secondary	Blood Pressure and Cardiovascular Risk biomarkers	Blood pressure, PAI-1 and VEGF will be measured.	Week 10 (end of treatment)	No
Secondary	Energy expenditure	Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits	Baseline	No
Secondary	Energy expenditure	Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits	Week 10 (end of treatment)	No
Secondary	Satiety	Satiety will be estimated by using a VAS questionnaire	Baseline	No
Secondary	Satiety	Satiety will be estimated by using a VAS questionnaire	Week 10 (end of treatment)	No
Secondary	Serum inflammation biomarkers	TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin	Baseline	No
Secondary	Serum inflammation biomarkers	TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin	Week 10 (end of treatment)	No
Secondary	Serum oxidative stress biomarkers	Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).	Baseline	No
Secondary	Serum oxidative stress biomarkers	Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).	Week 10 (end of treatment)	No
Secondary	Adipose tissue gene profile and function analysis	A biopsy (2 g) of subcutaneous abdominal periumbilical area adipose tissue will be obtained. In order to identify clusters/pathways of genes regulated by the supplementation of EPA and LA, microarray gene profiling will be performed in adipose tissue from the 4 groups after the nutritional intervention. If possible primary explant culture of adipose tissue biopsies will be also carried out.	Week 10 (end of treatment)	No
Secondary	Metabolomic and lipidomic profile	Samples of plasma and 24-h urine will be analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and Nuclear Magnetic Resonance (NMR), and Bidimensional Gas Chromatography-Mass Spectrometry (BC-MS).	Baseline	No
Secondary	Metabolomic and lipidomic profile	Samples of plasma and 24-h urine will be analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and Nuclear Magnetic Resonance (NMR), and Bidimensional Gas Chromatography-Mass Spectrometry (BC-MS).	Week 10 (end of treatment)	No

External Links

•   Department of Nutrition, Food Science, Physiology and Toxicology
•   European Master´s Degree in Feeding, Nutrition and Metabolism