Supplementation With PUFA´s in Obese Children (PUFA)

Effect of Two Omega 3 Polyunsaturated Fatty Acid Schemes on Insulin Resistance and the Inflammatory and Lipid Profile in Obese Children

Introduction. Insulin resistance (IR) accompanies practically half of children with obesity. This alteration is the border between what can be reversible or permanent. Among the comorbidities associated with IR are T2D and cardio and cerebrovascular diseases, which are the leading causes of death in Mexico. It has been said that the prevention of obesity rather than its treatment is the way to contain this problem. It has been proposed to supplement obese children with IR with ω-3 polyunsaturated fatty acids (PUFA) or ω-9 monounsaturated fatty acids (MUFA) to determine their ability to reverse these alterations.

Objetive. To evaluate the effect of supplementing PUFA ω-3, PUFA ω-9 or both, on the change in anthropometric and metabolic parameters in obese children with IR.

Methods. Clinical trial, randomized triple-blind, in which obese children with IR participated. Intervention. Three groups were integrated that received one of the following treatments for three months: Group 1: PUFA ω-3 1.8 g/day; Group 2: PUFA ω-3 0.9 g/day + PUFA ω-9 0.9 g/day (avocado oil). Group 3: MUFA ω-9 1.8 g/day. Tracing. For 2 more months he continued his clinical surveillance. Anthropometric and metabolic profile measurements were made at baseline, 3 and 5 months. Throughout the study, all three child groups received nutritional counseling, but no calorie-restricted diets or exercise programs were used.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Child Obesity; Metabolic Complication
• Intervention / Treatment: Dietary supplement: AGPI ω-3 (Triple Strength Fish Oil®); Dietary supplement: AGPI ω-3 + MUFA (avocado oil); Dietary supplement: MUFA (avocado oil) (1.8g)

Detailed Description

Specific objectives

1. To compare between the study groups, the concentrations of glucose, insulin and HOMA-IR Index, at baseline, at the end of supplementation with PUFA ω-3 and PUFA ω-9 (3 months) and 2 months after supplementation. the supplementation.
2. To compare between the study groups, the concentrations of total cholesterol, HDL cholesterol, LDL cholesterol and TG at baseline, at the end of supplementation and 2 months after supplementation.
3. To compare between the study groups the change in the percentile values of body mass index (BMI) and waist circumference (WC), between the study groups, at baseline, at the end of supplementation (3 months) and 2 months after supplementation.

Methods. A randomized, controlled, triple-blind clinical trial was conducted, which included 133 children with obesity (BMI ≥95th percentile) and with IR (HOMA-IR ≥ 3.0).

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 06720
    • Hospital Infantil de Mexico Federico Gomez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 13 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children with obesity (BMI ≥95 pc), according to the CDC reference tables.
• HOMA-IR ≥ 3.0.
• That they grant their written consent to participate.

Exclusion Criteria:

• Patients with any chronic disease.
• Patients who consume medications that alter their metabolic profile.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PUFA ω-3 (1.8g/day); ω-3 PUFAs (Triple Strength Fish Oil®) were purchased in advance, each capsule contained 540 mg of eicosapentaenoic acid (20:5 n-3) and 360 mg of docosahexaenoic acid (22:6 n-3), for a 0.9g total. Children and parents were told that they should take 2 capsules of ω-3 PUFAs daily, that is, they took 1.8g/day. Parents and children were informed that the duration of the study would be 5 months, in the first three months, the children should take the capsules of the assigned treatment; in the fourth and fifth months they should continue their surveillance with the researchers. At the beginning, they were given 2 bottles of 30 capsules each, identified as formula A or B, according to the assigned group, and they were given a calendar sheet indicating that they should cross out a box if they had consumed the breakfast capsule and cross out another box if the consumed during the meal; Likewise, they were asked to write down any adverse effect, if any, on the same sheet.	Dietary supplement: AGPI ω-3 (Triple Strength Fish Oil®); The children met at a clinical studies office every month for the 5 months, in order to exchange the empty bottles for the full ones and review the consumption record sheet and receive their advice on their diet. In case of absence, the children were located to avoid losses. Finally, at each visit, all the children and their parents received counseling to promote the acquisition of healthy habits related to eating and physical activity, but did not indicate caloric restriction diets or undergo exercise programs.
ACTIVE_COMPARATOR: PUFAs ω-3 0.9 g/day + MUFAs (avocado oil) 0.9 g/day.; A commercial brand of avocado oil (MUFA) was purchased in advance by putting 0.9g in each capsule. The appearance of the ω-3 PUFA capsules and the avocado oil capsules were the same. Then we worked with the company that prepared the blinding of the treatments, packaging bottles of 30 capsules each, labeling them as bottles A and B. The design contemplated giving each child two bottles, one marked to take it for breakfast and another marked to take it with food. The child was instructed to take 1 capsule per day of PUFA ω-3 (0.9g/d) and 1 capsule of avocado oil (0.9g/d)	Dietary supplement: AGPI ω-3 + MUFA (avocado oil); AGPI ω-3 (0.9g) + MUFA (avocado oil) (0.9g) The children met at a clinical studies office every month for the 5 months, in order to exchange the empty bottles for the full ones and review the consumption record sheet and receive their advice on their diet. In case of absence, the children were located to avoid losses. Finally, at each visit, all the children and their parents received counseling to promote the acquisition of healthy habits related to eating and physical activity, but did not indicate caloric restriction diets or undergo exercise programs.
PLACEBO_COMPARATOR: MUFAs (avocado oil) 1.8 g/day.; The child was instructed to take 2 capsules per day, 1.8g of avocado oil per day.	Dietary supplement: MUFA (avocado oil) (1.8g); MUFA (avocado oil) (1.8g) The children met at a clinical studies office every month for the 5 months, in order to exchange the empty bottles for the full ones and review the consumption record sheet and receive their advice on their diet. In case of absence, the children were located to avoid losses. Finally, at each visit, all the children and their parents received counseling to promote the acquisition of healthy habits related to eating and physical activity, but did not indicate caloric restriction diets or undergo exercise programs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in insulin resistance	Insulin concentrations were immunoassayed with MILLIPLEX® MAP, based on automated Luminex xMAP® technology. Luminex that uses microsphere techniques, which are coated with specific capture antibodies, and employs two fluorescent dyes. The bioassay result was quantified based on the fluorescence signals. The data was integrated and analyzed with the MILLIPLEX® Analyst 5.1 software. The following equation was used to obtain the homeostasis model to assess the index of insulin resistance (HOMA-IR): fasting glucose (mg/dl) x fasting insulin (μU/ml) / 405	Change in insulin resistance from baseline at 3 months
Change in insulin resistance	Insulin concentrations were immunoassayed with MILLIPLEX® MAP, based on automated Luminex xMAP® technology. Luminex that uses microsphere techniques, which are coated with specific capture antibodies, and employs two fluorescent dyes. The bioassay result was quantified based on the fluorescence signals. The data was integrated and analyzed with the MILLIPLEX® Analyst 5.1 software. The following equation was used to obtain the homeostasis model to assess the index of insulin resistance (HOMA-IR): fasting glucose (mg/dl) x fasting insulin (μU/ml) / 405	Change in insulin resistance from baseline at 5 months
Change in BMI percentile	Weight (kg) and height (cm) were taken using internationally accepted procedures and standardized per person. Briefly, weight and height were measured without shoes and in light clothing. Weight was taken with a digital scale (Seca 884, Hamburg, Germany) with a precision of 0.1 kg; height was measured using a stadiometer (Seca 225). With the values of weight, height, age and sex, the BMI percentile was obtained according to the CDC.	Change in BMI percentile from baseline at 3 months
Change in BMI percentile	Weight (kg) and height (cm) were taken using internationally accepted procedures and standardized per person. Briefly, weight and height were measured without shoes and in light clothing. Weight was taken with a digital scale (Seca 884, Hamburg, Germany) with a precision of 0.1 kg; height was measured using a stadiometer (Seca 225). With the values of weight, height, age and sex, the BMI percentile was obtained according to the CDC.	Change in BMI percentile from baseline at 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in waist circumference (percentile)	Waist circumference (cm) was measured with the children in a standing position, using a flexible tape measure (Seca 201®), placed at the midpoint between the lower rib and the iliac crest after a normal exhalation, according to the protocol of WHO. Using the tables of waist circumference of Mexican children, a very high risk was considered if the circumference was greater than the 90th percentile	Change in waist circumference percentile from baseline at 3 months
Change in waist circumference (percentile)	Waist circumference (cm) was measured with the children in a standing position, using a flexible tape measure (Seca 201®), placed at the midpoint between the lower rib and the iliac crest after a normal exhalation, according to the protocol of WHO. Using the tables of waist circumference of Mexican children, a very high risk was considered if the circumference was greater than the 90th percentile.	Change in waist circumference percentile from baseline at 5 months
Change in metabolic parameters (mg/dL)	Glucose (mg/dL), low-density lipoprotein (mg/dL), high-density lipoprotein (mg/dL), triglycerides (mg/dL), and total cholesterol (mg/dL) determinations were analyzed with enzymatic methods according to the procedures manual of the Central Laboratory of the Hospital Infantil de México Federico Gómez (Dimension-RXL, Dade Behring, Germany).	Change in metabolic parameters (mg/dL)from baseline at 3 months
Change in metabolic parameters (mg/dL)	Glucose (mg/dL), low-density lipoprotein (mg/dL), high-density lipoprotein (mg/dL), triglycerides (mg/dL), and total cholesterol (mg/dL) determinations were analyzed with enzymatic methods according to the procedures manual of the Central Laboratory of the Hospital Infantil de México Federico Gómez (Dimension-RXL, Dade Behring, Germany).	Change in metabolic parameters (mg/dL) from baseline at 5 months
Change in cytokines (pg/mL)	In serum, the following cytokines IL1B, IL4, IL_6, IL10, IFNg, MCP1, TNTa and Leptin (pg/mL) are determined. Based on automated Luminex xMAP® technology.	Change in cytokines (pg/mL) from baseline at 3 months
Change in cytokines (pg/mL)	In serum, the following cytokines IL1B, IL4, IL_6, IL10, IFNg, MCP1, TNTa and Leptin (pg/mL) are determined. Based on automated Luminex xMAP® technology.	Change in cytokines (pg/mL) from baseline at 5 months

Collaborators and Investigators

• Sponsor: Hospital Infantil de Mexico Federico Gomez
• Collaborators: Centro Universitario del Sur, Guadalajara; Instituto de Servicios Descentralizados de Salud Pública del Estado de Campeche
• Investigators: Principal Investigator: Jenny Vilchis Gil, PhD, Hospital Infantil de Mexico Federico Gomez

Publications and helpful links

General Publications

• Juarez-Lopez C, Klunder-Klunder M, Madrigal-Azcarate A, Flores-Huerta S. Omega-3 polyunsaturated fatty acids reduce insulin resistance and triglycerides in obese children and adolescents. Pediatr Diabetes. 2013 Aug;14(5):377-83. doi: 10.1111/pedi.12024. Epub 2013 Feb 25.
• Juarez-Lopez C, Klunder-Klunder M, Medina-Bravo P, Madrigal-Azcarate A, Mass-Diaz E, Flores-Huerta S. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents. BMC Public Health. 2010 Jun 7;10:318. doi: 10.1186/1471-2458-10-318.
• Vilchis-Gil J, Galvan-Portillo M, Klunder-Klunder M, Cruz M, Flores-Huerta S. Food habits, physical activities and sedentary lifestyles of eutrophic and obese school children: a case-control study. BMC Public Health. 2015 Feb 11;15:124. doi: 10.1186/s12889-015-1491-1.

Helpful Links

• This page is from the Hospital Infantil de México Federico Gómez where the research protocol was approved and developed.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 17, 2014
• Primary Completion (ACTUAL): December 16, 2015
• Study Completion (ACTUAL): September 26, 2016

Study Registration Dates

• First Submitted: August 1, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (ACTUAL): August 4, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: obesity; insulin resistance; child; metabolic profile; PUFA ω-3
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Pediatric Obesity; Insulin Resistance
• Other Study ID Numbers: HIM/2013/0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be shared once the statistical analyzes are carried out and it is sent for publication.
• IPD Sharing Time Frame: When the study is published, the database will be available in the journal indefinitely.
• IPD Sharing Access Criteria: Access to the database through the journal where it is published, in the supplementary files section
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No