Effect of Speed of Weight Loss on Compensatory Mechanisms Activated During Weight Reduction

Study Overview
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Brief Summary
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Obesity has become a global epidemic with huge public health implications. Although clinical significant weight loss (WL) can be achieved by a combination of diet and behavioral modification, strong metabolic adaptations, with increased appetite and suppressed energy expenditure, are activated, which compromise WL maintenance and increase the risk of relapse. The aim of this project is to investigate the potential role of WL rate in modulating such responses. More specifically, the investigators want to determine if a similar WL achieved rapidly vs slowly induce the same compensatory responses to weight reduction. A secondary aim is to assess if speed of weight loss can influence motivation. A large battery of assessments will be performed before and after weight reduction including body composition, resting metabolic rate, substrate oxidation, exercise efficiency, fasting and postprandial release of several appetite-regulating hormones, subjective feelings of hunger and fullness and motivation. This project can bring large practical benefits concerning the design of weight loss programs to minimize weight relapse.

Official Title
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Effect of Speed of Weight Loss on Compensatory Mechanisms Activated During Weight Reduction

Conditions
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Obesity

Intervention / Treatment
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* Behavioral: Very-low calorie diet (VLCD)
* Behavioral: Low calorie diet (LCD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (18-50 years old) Obese healthy volunteers (30<BMI<45 kg/m2) Weight stable on the last three months (<2kg), not currently dieting to lose weight and with an inactive lifestyle) Exclusion Criteria: History of endocrine/cardiovascular/pulmonary/kidney disease, anaemia, gout, milk intolerance, depression or other psychological disorders, eating disorders, drug or alcohol abuse within the last two years and current medication known to affect appetite or induce weight loss. Those with a planned surgery during the study period or participating in another research study will also not be accepted to take part in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapid weight loss group<br>The rapid weight loss group will follow a commercial very-low calorie diet (VLCD) during 4 weeks. The participants allocated to this group will follow a 550 (women) - 660 (men) kcal/day diet. The VLCD products provide 110kcal/pack and include a variety of milkshakes, smoothies and soups. In addition to VLCD products, calorie-free drinks and some low-starch vegetables (maximum 2 cups/day) will be allowed. Drinking at least 2.5 liters of non-caloric liquids will be recommended. | Behavioral: Very-low calorie diet (VLCD)<br> <br> |
| Experimental: Slow weight loss group<br>The slow weight loss group will be prescribed an individualized low calorie diet (LCD) (1200-1500kcal/day), during 8 weeks, using meal replacements (such as smoothies, soups and cereal bars) and conventional foods. The macronutrient composition will be matched with that of the VLCD. | Behavioral: Low calorie diet (LCD)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appetite related hormones | Appetite-related hormones (active ghrelin, PYY, GLP-1, CCK) will be measured in fasting and every 30 minutes up to 2,5 hours | Before the start of the study and again at week 2 and 4 (VLCD group) and 4 and 8 (LCD group). And also, on week 12 (for both groups). | 
| Body composition | Body composition measured by air displacement plethysmography | Baseline, 2 and 4 weeks (VLCD group) and 4 and 8 weeks (LCD group) and 12 weeks (both groups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting metabolic rate (RMR) | RMR measured by indirect calorimetry | Baseline, 2 and 4 weeks (VLCD group) and 4 and 8 weeks (LCD group) and 12 weeks (both groups) | 
| Exercise efficiency | Exercise efficiency measured by graded exercise on a bike | Baseline, 2 and 4 weeks (VLCD group) and 4 and 8 weeks (LCD group) and 12 weeks (both groups) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight loss, Speed of weight loss, Metabolic compensation, Diet therapy