search
Back to results

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

Primary Purpose

Obesity, Body Fat, Insulin Resistance

Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Double blind dietary intervention with EPA and lipoic acid
Sponsored by
Clinica Universidad de Navarra, Universidad de Navarra
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity focused on measuring Obesity, Calorie restriction, Eicosapentaenoic acid (EPA), Lipoic acid, Weight loss, Insulin sensitivity, Lipid metabolism, Adipokines, Inflammation, Oxidative stress, Adipose tissue gene profile, Metabolomic profile

Eligibility Criteria

20 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

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)

Sites / Locations

  • Department of Nutrition, Food Science, Physiology and Toxicology. University of Navarra

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Control group

EPA group

Lipoic acid group

EPA+LA group

Arm Description

Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + placebos supplements

Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + EPA (1.3 g/day, 3 capsules of 433 mg/day) supplement (EPA Group).

Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + LA (300 mg/day, 3 capsules of 100 mg/day) supplement (LA Group)

Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + EPA/LA (1.3 g /day and 300 mg/day respectively).

Outcomes

Primary Outcome Measures

Weight Loss
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Weight Loss
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Weight Loss
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Weight Loss
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Weight Loss
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Weight Loss
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
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.
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.
Glucose metabolism parameters
Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index
Glucose metabolism parameters
Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index
Lipid metabolism biomarkers
Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies.
Lipid metabolism biomarkers
Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies.

Secondary Outcome Measures

Blood Pressure and Cardiovascular Risk biomarkers
Blood pressure, PAI-1 and VEGF will be measured.
Blood Pressure and Cardiovascular Risk biomarkers
Blood pressure, PAI-1 and VEGF will be measured.
Energy expenditure
Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits
Energy expenditure
Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits
Satiety
Satiety will be estimated by using a VAS questionnaire
Satiety
Satiety will be estimated by using a VAS questionnaire
Serum inflammation biomarkers
TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin
Serum inflammation biomarkers
TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin
Serum oxidative stress biomarkers
Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).
Serum oxidative stress biomarkers
Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).
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.
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).
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).

Full Information

First Posted
May 21, 2010
Last Updated
May 27, 2015
Sponsor
Clinica Universidad de Navarra, Universidad de Navarra
search

1. Study Identification

Unique Protocol Identification Number
NCT01138774
Brief Title
Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) in Human Obesity
Acronym
OBEPALIP
Official Title
Cellular and Molecular Effects of Lipoic Acid and Eicosapentaenoic Acid (EPA) on Adipose Tissue: Potential Application in Human Obesity
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clinica Universidad de Navarra, Universidad de Navarra

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Body Fat, Insulin Resistance
Keywords
Obesity, Calorie restriction, Eicosapentaenoic acid (EPA), Lipoic acid, Weight loss, Insulin sensitivity, Lipid metabolism, Adipokines, Inflammation, Oxidative stress, Adipose tissue gene profile, Metabolomic profile

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
103 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + placebos supplements
Arm Title
EPA group
Arm Type
Experimental
Arm Description
Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + EPA (1.3 g/day, 3 capsules of 433 mg/day) supplement (EPA Group).
Arm Title
Lipoic acid group
Arm Type
Experimental
Arm Description
Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + LA (300 mg/day, 3 capsules of 100 mg/day) supplement (LA Group)
Arm Title
EPA+LA group
Arm Type
Experimental
Arm Description
Dietary treatment with a calorie restriction of 30 % the subject's energy expenditure at baseline + EPA/LA (1.3 g /day and 300 mg/day respectively).
Intervention Type
Dietary Supplement
Intervention Name(s)
Double blind dietary intervention with EPA and lipoic acid
Intervention Description
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).
Primary Outcome Measure Information:
Title
Weight Loss
Description
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Time Frame
Week 0 (baseline)
Title
Weight Loss
Description
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Time Frame
Week 2
Title
Weight Loss
Description
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Time Frame
Week 4
Title
Weight Loss
Description
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Time Frame
week 6
Title
Weight Loss
Description
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Time Frame
Week 8
Title
Weight Loss
Description
Volunteers will attend the Nutritional Intervention unit (University of Navarra), where their weight will be measured to the nearest 0.1 kg.
Time Frame
Week 10 (end of treatment)
Title
Body composition and Anthropometric parameters
Description
Changes in body composition will be analyzed by Dual X-ray Absorptiometry (DXA) and by bioimpedance, and hip and waist circumferences will be measured.
Time Frame
Week 0 (Baseline)
Title
Body composition and anthropometric parameters
Description
Changes in body composition will be analyzed by Dual X-ray Absorptiometry (DXA) and by bioimpedance, and hip and waist circumferences will be measured.
Time Frame
Week 10 (end of treatment)
Title
Glucose metabolism parameters
Description
Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index
Time Frame
Week 0 (baseline)
Title
Glucose metabolism parameters
Description
Fasting serum glucose, Fasting serum insulin, Oral Glucose Tolerance Test, HOMA index
Time Frame
Week 10 (end of treatment)
Title
Lipid metabolism biomarkers
Description
Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies.
Time Frame
Week 0 (baseline)
Title
Lipid metabolism biomarkers
Description
Serum total-cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, free fatty acids, ketone bodies.
Time Frame
Week 10 (end of treatment)
Secondary Outcome Measure Information:
Title
Blood Pressure and Cardiovascular Risk biomarkers
Description
Blood pressure, PAI-1 and VEGF will be measured.
Time Frame
Baseline
Title
Blood Pressure and Cardiovascular Risk biomarkers
Description
Blood pressure, PAI-1 and VEGF will be measured.
Time Frame
Week 10 (end of treatment)
Title
Energy expenditure
Description
Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits
Time Frame
Baseline
Title
Energy expenditure
Description
Energy expenditure will be estimated by indirect calorimetry, and T3, T4 and TSH levels will be analysed by ELISA kits
Time Frame
Week 10 (end of treatment)
Title
Satiety
Description
Satiety will be estimated by using a VAS questionnaire
Time Frame
Baseline
Title
Satiety
Description
Satiety will be estimated by using a VAS questionnaire
Time Frame
Week 10 (end of treatment)
Title
Serum inflammation biomarkers
Description
TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin
Time Frame
Baseline
Title
Serum inflammation biomarkers
Description
TNF-alpha, IL-6, C-reactive protein, serum A-amiloid, Leptin, Adiponectin, Visfatin
Time Frame
Week 10 (end of treatment)
Title
Serum oxidative stress biomarkers
Description
Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).
Time Frame
Baseline
Title
Serum oxidative stress biomarkers
Description
Total and Reduced Glutathione, Glutathione Peroxidase, MDA, Superoxide Dismutase-2 (Mn-SOD).
Time Frame
Week 10 (end of treatment)
Title
Adipose tissue gene profile and function analysis
Description
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.
Time Frame
Week 10 (end of treatment)
Title
Metabolomic and lipidomic profile
Description
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).
Time Frame
Baseline
Title
Metabolomic and lipidomic profile
Description
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).
Time Frame
Week 10 (end of treatment)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria J Moreno-Aliaga, PhD
Organizational Affiliation
University of Navarra
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alfredo Martínez, PhD
Organizational Affiliation
University of Navarra
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Santiago Navas-Carretero, PhD
Organizational Affiliation
University of Navarra
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Nutrition, Food Science, Physiology and Toxicology. University of Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
19588730
Citation
Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Barber A, Martinez 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. doi: 10.1007/BF03165968.
Results Reference
background
PubMed Identifier
20352620
Citation
Lorente-Cebrian 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.
Results Reference
background
PubMed Identifier
19296827
Citation
Lorente-Cebrian 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.
Results Reference
background
PubMed Identifier
18829285
Citation
Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Marti A, Martinez 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.
Results Reference
background
PubMed Identifier
18807107
Citation
Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Baena MJ, Marti A, Martinez 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.
Results Reference
background
PubMed Identifier
18755047
Citation
Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Martinez 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.
Results Reference
background
PubMed Identifier
17298710
Citation
Perez-Matute P, Perez-Echarri N, Martinez 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. doi: 10.1017/S0007114507207627.
Results Reference
background
PubMed Identifier
16900083
Citation
Marrades MP, Martinez 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. doi: 10.1038/sj.ejcn.1602500. Epub 2006 Aug 9.
Results Reference
background
PubMed Identifier
16325777
Citation
Marrades MP, Milagro FI, Martinez 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. doi: 10.1016/j.bbrc.2005.11.080. Epub 2005 Nov 22.
Results Reference
background
PubMed Identifier
18491071
Citation
Ramel A, Martinez 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.
Results Reference
background
PubMed Identifier
18602429
Citation
Parra D, Ramel A, Bandarra N, Kiely M, Martinez 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.
Results Reference
background
PubMed Identifier
19487105
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.
Results Reference
background
PubMed Identifier
19210857
Citation
Navas-Carretero S, Perez-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.
Results Reference
background
PubMed Identifier
29743087
Citation
Romo-Hualde A, Huerta AE, Gonzalez-Navarro CJ, Ramos-Lopez O, Moreno-Aliaga MJ, Martinez JA. Untargeted metabolomic on urine samples after alpha-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women. Lipids Health Dis. 2018 May 9;17(1):103. doi: 10.1186/s12944-018-0750-4.
Results Reference
derived
PubMed Identifier
26962183
Citation
Huerta AE, Prieto-Hontoria PL, Sainz N, Martinez JA, Moreno-Aliaga MJ. Supplementation with alpha-Lipoic Acid Alone or in Combination with Eicosapentaenoic Acid Modulates the Inflammatory Status of Healthy Overweight or Obese Women Consuming an Energy-Restricted Diet. J Nutr. 2015 Apr 1;146(4):889S-896S. doi: 10.3945/jn.115.224105.
Results Reference
derived
Links:
URL
http://www.unav.es/master/nutricion-metabolismo/
Description
European Master´s Degree in Feeding, Nutrition and Metabolism

Learn more about this trial

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

We'll reach out to this number within 24 hrs