Supplementation With PUFA´s in Obese Children

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
Specific objectives 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. 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. 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).

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

Conditions
-----------------
Child Obesity, Insulin Resistance, 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)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 13 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Subject to written informed consent, children who agreed to participate were randomly assigned to the following treatment groups. Group 1. Two daily capsules of ω-3FAs; Group 2. Two daily capsules, one of ω-3FAs of 0.9 g + 1 capsule of avocado oil (AcAg) of 0.9 g and; Group 3. Two daily capsules of 0.9 g of AcAg.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PUFA ω-3 (1.8g/day)<br>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®)<br>* 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.<br>|
| Active Comparator: PUFAs ω-3 0.9 g/day + MUFAs (avocado oil) 0.9 g/day.<br>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)<br>* 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.<br>|
| Placebo Comparator: MUFAs (avocado oil) 1.8 g/day.<br>The child was instructed to take 2 capsules per day, 1.8g of avocado oil per day. | Dietary Supplement: MUFA (avocado oil) (1.8g)<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, child, insulin resistance, metabolic profile, PUFA ω-3