EPICO: (Study for the Pro-resolution of Chronic Inflammation in Obesity. Original Acronym From Spanish)

Sponsor

University of Guadalajara (Other)

Overall Status

Recruiting

CT.gov ID

NCT05068557

Collaborator

(none)

Enrollment

Location

Arms

2.2

Anticipated Duration (Months)

35.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Omega-3 fatty acids, especially EPA and DHA have long been acknowledged for their capacity to counteract inflammatory responses in the human body. Understanding the impact of the dietary intake of these fatty acids along with others (such as ARA) involved in inflammation is essential for prevention and treatment of chronic non-communicable diseases as it is obesity and its comorbidities.

The role that the EPA and DHA play in the inflammatory processes can be understood by studying the capacity of certain immune cells and their genetic background to respond under the constant exposure to an adjusted diet in omega-6/omega-3 fatty acids in individuals with obesity.

Condition or Disease	Intervention/Treatment	Phase
Obesity Chronic Inflammation	Dietary Supplement: Dietary plan along with fish oil capsules (3 capsules daily. Containing EPA+DHA: 1.8 g). Dietary Supplement: Dietary plan along with chia/linseed oil capsules (3 capsules daily. Containing ALA 1.6 g).	N/A

Detailed Description

A total of 80 subjetcs will be invited to be enrolled in a nutrigenomics/nutrigenetics study approaching the properties of a dietary plan (mild calorie restriction and adjusted at an omega-6/omega-3 fatty acids ratio of 4:1, and supplemented with fish oil rich in EPA and DHA or placebo).

This double blind, randomized, parallel clinical trial will consist in a 12-week intervention with recurrent visits every 4 weeks. Subjects will be required to follow the dietary plan provided in a recipee book produced and edited by our research group along with a capsule in every major meal (breakfast, lunch, and dinner) for 12 weeks. In every visit, all subects will undergo a body composition analysis as well as blood tests that include: total cell count, glucose and lipid homeostasis, serum inflammatory markers, DNA extraction for genetic tests (SNPs involved in inflammation), isolation and ex vivo stimulation of neutrophils, determination of and isolation of PBMCs for further analysis of gene expression and protein abundance.

This study proposes three distinct but closely related approaches for reaching a further understanding of the actions of EPA and DHA intake:

Through the conversion of EPA and DHA to specialized pro-resolving mediators (SPMs) such as resolvins (E and D) determined by an ex vivo assay
Through the study of the involved enzyme coding-genes in the previously mentioned conversion
Through the study of the activation of specific membrane receptors (FFAR4)

All these approaches will have in common the correlation with serum inflammatory markers (TNF alpha, MCP1, IL-6, and IL-10).

Once the project is finished, the research strategies for new studies will be improved. In the same way, the application of the knowledge generated in it will be encouraged towards the health care of patients with obesity who could attend our service on future occasions. Finally, we would disseminate the knowledge generated in our institutional community, which would increase the impact of the project.

In summary, the impact is divided into the following points:

Identification of genetic markers relevant to the treatment of obesity and its comorbidities
Bases for new strategies aimed at reducing chronic low-grade inflammation inherent in obesity
Useful information on gene-nutrient interaction for the public and private sector in the field of genetic testing
Study population benefited from the results of the intervention and the information of their genetic and biochemical profiles Data from this study would strengthen the inflammatory knowledge of obesity comorbidities from distinct standpoints

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind randomized parallel clinical trialDouble-blind randomized parallel clinical trial

Masking:

Double (Participant, Investigator)

Masking Description:

Both type of capsules were deposited in equally labeled flaks under sterile conditions. Every flask was identified and tagged with a specific number by an associate researcher who is not involved in the recruitment, attention, or follow-up of the enrolled subjects. Finally, block randomization was the selected technique for this purpose.

Primary Purpose:

Treatment

Official Title:

Dietary Intervention Supplemented With PUFA Omega-3 Fatty Acids on the Pro-resolving Capacity in Subjects With Obesity.

Actual Study Start Date :

Sep 24, 2021

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention group Dietary plan with a mild calorie restriction and adjusted in PUFA omega-3/omega-6 ratio (4:1) along with fish oil (3 capsules daily. Containing EPA+DHA: 1.8 g). (n=40)	Dietary Supplement: Dietary plan along with fish oil capsules (3 capsules daily. Containing EPA+DHA: 1.8 g). Subects within the Intervention group will be provided with a dietary plan along with fish oil capsules. Subjects will be asked to consume three capsules per day. Every capsule contains: EPA+DHA: 1.8 g. Other Names: Dietary intervention along with fish oil
Placebo Comparator: Control group Dietary plan with a mild calorie restriction and adjusted in PUFA omega-3/omega-6 ratio (4:1) along with chia/linseed oil (3 capsules daily. Containing ALA 1.6 g). (n=40)	Dietary Supplement: Dietary plan along with chia/linseed oil capsules (3 capsules daily. Containing ALA 1.6 g). Subects within the Intervention group will be provided with a dietary plan along with fish oil capsules. Subjects will be asked to consume three capsules per day. Every capsule contains: ALA 1.6 g). Other Names: Placebo

Arm

Intervention/Treatment

Active Comparator: Intervention group

Dietary plan with a mild calorie restriction and adjusted in PUFA omega-3/omega-6 ratio (4:1) along with fish oil (3 capsules daily. Containing EPA+DHA: 1.8 g). (n=40)

Dietary Supplement: Dietary plan along with fish oil capsules (3 capsules daily. Containing EPA+DHA: 1.8 g).

Subects within the Intervention group will be provided with a dietary plan along with fish oil capsules. Subjects will be asked to consume three capsules per day. Every capsule contains: EPA+DHA: 1.8 g.

Other Names:

Dietary intervention along with fish oil

Placebo Comparator: Control group

Dietary plan with a mild calorie restriction and adjusted in PUFA omega-3/omega-6 ratio (4:1) along with chia/linseed oil (3 capsules daily. Containing ALA 1.6 g). (n=40)

Dietary Supplement: Dietary plan along with chia/linseed oil capsules (3 capsules daily. Containing ALA 1.6 g).

Subects within the Intervention group will be provided with a dietary plan along with fish oil capsules. Subjects will be asked to consume three capsules per day. Every capsule contains: ALA 1.6 g).

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

Resolvin E1 and D1 secretion under stimulation conditions (ex vivo). [12 weeks]
Stimulation of neutrophils from subjects who underwent a dietary plan (mild calorie restriction along with an omega-6/omega-3 adjusted ratio and supplemented with fish oil or placebo) and their correlation with inflammatory markers (serum TNF alpha, IL-6, MCP1, and IL-10). The major markers of change are resolvin E1 and resolvin D1 (RvE1 and RvD1).
Genetic analysis of Single Nucleotide Polymorphism (SNPs) involved in the synthesis of specialized pro-resolving mediators (SPMs). [12 weeks]
Subjects who underwent a dietary plan (mild calorie restriction along with an omega-6/omega-3 fatty acids adjusted ratio and supplemented with fish oil or placebo) will be genotyped based on inflammatory genetic variants: CYP4F3 (rs1805042), PTGS2 (rs5275, rs20417, and rs689466) y ALOX15 (rs11568131) and their correlation with the (ex vivo) secretion of Resolvin E1 and D1 and with inflammatory markers (serum TNF alpha, IL-6, MCP1, and IL-10).
Analysis of the activation of FFAR4 in PBMCs [12 weeks]
Analysis through immunoprecipitation and immunoblotting to determine the activation of FFAR4 in PBMCs and their correlation with inflammatory markers (serum TNF alpha, IL-6, MCP1, and IL-10). Subjects who underwent a dietary plan (mild calorie restriction along with an omega-6/omega-3 fatty acids adjusted ratio and supplemented with fish oil or placebo)

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

25-59 years of age, both sexes
Subjects who agree to participate in the study and all signed informed consent
BMI 30 kg/m2 - 39.9 kg/m2
Waist circumference >88 cm for females; >102 cm for males

Exclusion Criteria:

Currently consuming any of the following drugs: NSAIDS, anticoagulants, hypoglycemic, oR hypolipemic drugs
Diagnosed autoimmune diseases
Diagnosed cancer
Pregnancy and breastfeeding
Allergy to chia, linseed or fish oil
Subjects who wish to abandon the study