Effect of Nutritional Intervention and Olive Oil in Severe Obesity

Study Overview
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Brief Summary
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Obesity is a worldwide epidemic with increasing prevalence, specially severe obesity (Body Mass Index (BMI) ≥ 35 kg/m2). It is a multifactorial disease that involves genetic and environmental factors that lead to increased mortality from cardiovascular disease, diabetes, cancer, among others and impairs life quality. Most research on severe obesity focuses on surgical alternatives and their results, thus this clinical trial aims to evaluate the effect of a non-pharmacological approach based on nutritional intervention and supplementation with a functional food, the olive oil. It will analyze the effectiveness of interventions on: weight loss, improvements on body composition and inflammatory profile (TNF-alfa, interleucins 1, 6 and 10, adiponectin), insulin resistance and serum lipids control, changing eating habits and physical activity practice, modification on bone mineral density and sarcopenia, and reduction of cardiovascular risk and other diseases. Also, it will be investigated the influence of polymorphisms (Pro12Ala of PPAR-γ gene, -174G>C of IL6 gene e Trp64Arg of ADRB3 gene) on nutritional intervention effectiveness with and without olive oil. This research looks for improving severely obese patient's care and contributing to effective results by reducing costs and risk treatment. The investigators believe that this informations will contribute significantly to the scientific field, expanding the knowledge about severe obesity.

Detailed Description
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After enrollment, patients undergo a diagnostic phase (baseline) with nutritional, anthropometric and body composition assessment (multifrequency bioelectrical impedance analysis and dual X-ray absorptiometry); investigation of clinical history; collecting blood samples; carotid artery intima-media thickness, heart rate variability and accelerometry assessments; and application of validated questionnaires to evaluate secondary outcomes. Patients will be randomized into three different treatment groups. Randomization will be stratified according to Body Mass Index (BMI) (BMI between 35 and 39,99 kg/m2 and BMI ≥ 40 kg/m2), allocation ratio 1:1:1 and parallel intervention. Then, trained nutritionists will deliver the intervention according to the patient group and they will be followed-up for 12 weeks, with visits each 4 weeks. Interventions will be provided as follow: Olive oil group: in order to evaluate the effect of only the extra virgin olive oil on primary and secondary outcomes, patients will be instructed to maintain habitual food consumption and consume 52 mL of extra virgin olive oil daily (4 sachets per day, 2 at lunch and 2 at dinner). Nutritional intervention group: patients assigned to this group will receive nutritional intervention consisting of prescription of individualized food plan to reduce 5 to 10% of initial body weight, nutritional counseling for comorbidities and promoting healthy eating habits and physical activity. Resting Energy Expenditure (REE) will be calculated according to Horie-Waitzberg & Gonzalez equation developed for severe obese individual using current weight and lean body mass (Horie et al., 2011). Total energy expenditure (TEE) will be calculated multiplying REE by activity factor recommended by Institute of Medicine (Trumbo et al., 2005) and thermic effect of food (Hill, Wyat, Peters, 2012). Total energy value (TEV) of diet will be determined reducing 550 to 1100 kcal from TEE to reach 0.5 to 1.0 weekly weight reduction according to the patient's individual goal. Distribution of macronutrients will follow Dietary Reference Intake (DRI) recommendation: 45-65% of carbohydrates, 10-35% of proteins and 20-35% of lipids (Trumbo et al., 2002). Fat acids (FA) will be distributed as recommended by Sociedade Brasileira de Cardiologia (Sposito et al., 2007): ≤ 7% saturated FA, ≤ 20% monounsaturated FA and ≤ 7% polyunsaturated FA. Food plan prescription will distribute TEV in 4-6 meals. Motivation will be held to changing eating and lifestyle habits. Nutritional intervention plus olive oil: this group will receive conventional intervention plus supplementation of 52 mL of extra virgin olive oil daily (4 sachets per day, 2 at lunch and 2 at dinner). At the end of follow-up the same assessments performed at diagnostic phase will be held. To detect a reduction of 10 kg, with standard deviation of 30, which is in agreement with the study of Rodrigues e Silveira (2011), with a two-sided 5% significance level and a power of 80%, a sample size of 50 patients per group will be necessary, given an anticipated dropout rate of 42,9%. This research will be conducted at a capital of center Brazil, at Unidade de Pesquisa Clínica of Hospital das Clínica/UFG, Faculty of Medicine/UFG.

Official Title
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Effect of Nutritional Intervention and Olive Oil in Severe Obesity: Randomized Controlled Trial

Conditions
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Severe Obesity

Intervention / Treatment
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* Behavioral: Nutritional intervention
* Other: Nutritional intervention plus olive oil
* Dietary Supplement: Olive oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index ≥ 35 kg/m2 Residence in Goiânia or metropolitan area Patients referred by Secretaria Municipal de Saúde to Severe Obese Nutrition Clinic Exclusion Criteria: To have already performed bariatric surgery Pregnancy Reduction greater than 8% of body weight in the past 3 months To have been treated at Severe Obesity Nutrition Clinic or have received nutritional counseling in another place in the last 2 years Anti-obesity drugs use Regular utilization of anti-inflammatory drugs or corticosteroids HIV/AIDS, heart failure, kidney failure, hepatic insufficiency, chronic obstructive pulmonary disease and cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nutritional intervention<br>Patients under only nutritional intervention for weight loss | Behavioral: Nutritional intervention<br>* Conventional treatment (Nutritional intervention) consists of prescription of individualized food plan to reduce 5 to 10% of initial body weight, nutritional counseling for comorbidities and promoting healthy eating habits and physical activity.<br>|
| Experimental: Nutritional intervention plus olive oil<br>Patients under conventional treatment (nutritional intervention) plus extra virgin olive oil supplementation | Other: Nutritional intervention plus olive oil<br>* Nutritional intervention consists of prescription of individualized food plan to reduce 5 to 10% of initial body weight, nutritional counseling for comorbidities and promoting healthy eating habits and physical activity. Additionally, dietary supplementation with extra virgin olive oil (52 mL daily) will be held, divided in four (4) sachets per day, two (2) at lunch and two (2) at dinner.<br>|
| Experimental: Olive oil<br>Patient under habitual food consumption plus extra virgin olive oil supplementation | Dietary Supplement: Olive oil<br>* Patients will be instructed to maintain habitual food consumption and consume 52 mL of extra virgin olive oil daily in four (4) sachets per day, two (2) at lunch and two (2) at dinner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anthropometric measurements change | Measurements of weight, arm circumference and Body Mass Index (BMI) will be evaluated to assess anthropometric change. | Baseline, week 12 | 
| Body composition change | Body fat mass (BFM), body fat percentage (%BF) and body mass density (BMD) will be evaluated to assess body composition change. BFM and %BF will be assessed using multifrequency bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DXA) and BMD will be assessed using DXA. | Baseline, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inflammation parameters | TNF-alfa | Baseline, week 12 | 
| Change in inflammation parameters | Interleucin 6 (IL6), IL1, IL10 | Baseline, week 12 | 
| Change in inflammation parameters | Adiponectin | Baseline, week 12 | 
| Change in inflammation parameters | C-reactive protein (CRP) | Baseline, week 12 | 
| Change in inflammation parameters | Neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) | Baseline, week 12 | 
| Change in metabolic parameters | Lipid profile (total cholesterol, LDL-c, HDL-c, VLDL-c), insulin resistance (HOMA-IR, glycated hemoglobin), fasting glycaemia, hemogram | Baseline, week 12 | 
| Change in kidney function | Creatinine, urea and uric acid | Baseline, week 12 | 
| Change in liver function | AST and ALT | Baseline, week 12 | 
| Change in thyroid function | TSH, T4 and parathyroid hormone | Baseline, week 12 | 
| Change in vitamins | Vitamin D, vitamin B12 and folic acid | Baseline, week 12 | 
| Change in minerals | Iron, calcium, sodium, potassium and zinc | Baseline, week 12 | 
| Change in cardiovascular risk using Global Risk Score (GRS) |  | Baseline, week 12 | 
| Change in cardiovascular risk using Framingham Risk Score (FRS) |  | Baseline, week 12 | 
| Change in cardiovascular risk using heart rate variability (HRV) |  | Baseline, week 12 | 
| Change in cardiovascular risk using Homocystein level |  | Baseline, week 12 | 
| Polymorphism Pro12Ala of Peroxisome Proliferator-Activated Receptor Alfa (PPAR-alfa) | Difference in responses between intervention groups for anthropometric measurements (weight, arm circumference and body mass index) and body composition variables (body fat mass and body fat percentage) according to this polymorphism | Baseline, week12 | 
| PolymorphismTrp64Arg of Beta-3 Adrenergic Receptor (ADRB3) gene | Difference in responses between intervention groups for anthropometric measurements (weight, arm circumference and body mass index) and body composition variables (body fat mass and body fat percentage) according to this polymorphism | Baseline, week12 | 
| Polymorphism -174G>C of Interleukin 6 (IL6) gene. | Difference in responses between intervention groups for anthropometric measurements (weight, arm circumference and body mass index) and body composition variables (body fat mass and body fat percentage) according to this polymorphism | Baseline, week12 | 
| Change in physical activity practice using Global Physical Activity Questionnaire |  | Baseline, week 12 | 
| Change in physical activity practice using accelerometry |  | Baseline, week 12 | 
| Change in food intake using Food Frequency Questionnaire |  | Baseline, week 12 | 
| Change in food intake using 24 hour recall |  | Baseline, week 12 | 
| Change in bone health parameters | Change in the following variables: bone density using DXA, falls and fractures and sun exposure | Baseline, week 12 | 
| Change in obesity sarcopenia using muscle mass (evaluated using DXA) |  | Baseline, week 12 | 
| Change in obesity sarcopenia using handgrip strength |  | Baseline, week 12 | 
| Change in sarcopenia using usual gait speed |  | Baseline, week 12 | 
| Adherence to nutritional intervention | It will be evaluated through changes in food consumption (food frequency questionnaire) | Baseline, week 12 | 
| Adherence to the health service | It will be evaluated through attendance to the clinic visits | Baseline, week 12 | 
| Change in symptoms of anxiety and depression using Hospital Anxiety and Depression Scale |  | Baseline, week 12 | 
| Change in symptoms of binge eating disorderusing Binge Eating Disorder Scale |  | Baseline, week 12 | 
| Change in musculoskeletal pain using Visual Analog Scale |  | Baseline, week 12 | 
| Change in musculoskeletal pain using Nordic Musculoskeletal Questionnaire |  | Baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nutritional management, olive oil, weight loss, body composition, nutrigenomics, polymorphisms, cardiovascular risk, sarcopenia, inflammation, food intake, sedentary lifestyle, patient adherence, bone density