Hormonal Regulation of Body Weight Maintenance

Study Overview
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Brief Summary
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The investigators here propose to perform a collaborative clinical research effort including a randomized controlled trial investigating the mechanisms of weight maintenance and their relation to a lifestyle intervention in children, adolescents and adults. The detailed investigation and analysis of the variability and dynamics of the endocrine circuits responding to a negative energy balance and weight loss will be accompanied and enhanced by specific clinical projects targeting peripheral and central-nervous aspects of hormonal counter-regulation after weight loss. Mechanisms of endocrine counter-regulation and potential therapeutic approaches will be studied.

Official Title
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Hormonal Regulation of Body Weight Maintenance

Conditions
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Obesity, Weight Loss, Weight Gain, Hormone Disturbance, Adipose Tissue, Insulin Resistance, Skeletal Muscle

Intervention / Treatment
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* Behavioral: multimodal lifestyle intervention
* Behavioral: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI > 27 kg/m2 (adults) Exclusion Criteria: weight loss of more than 5kg in the last 2 months pregnancy, breastfeeding patients with: severe heart failure impaired hepatic or renal function anaemia disturbed coagulation (biopsies will not be taken in those subjects) infection, malabsorption severe hypertension cancer within the last 5 years eating disorders or any other psychiatric condition that would interact with the trial intervention any other endocrine disorder changes of smoking habits or diets within the last 3 months prior to study inclusion

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 90 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 |
| --- | --- |
| Placebo Comparator: placebo<br>Placebo | Behavioral: placebo<br>* no intervention, only follow up<br>|
| Experimental: lifestyle intervention<br>After an initial weight loss, the weight regain will be measured during multimodal lifestyle intervention in children, adolescents and adults | Behavioral: multimodal lifestyle intervention<br>* After an initial weight loss, the weight regain will be measured during multimodal lifestyle intervention in children, adolescents and adults<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI will be assessed during lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo | BMI (kg/m2) will be analyzed after intentional weight loss in two comparable parts of a randomized controlled trial including (1) children and adolescents and (2) adults. Therefore effects of a multimodal lifestyle intervention will be compared to placebo. | 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of leptin during lifestyle intervention | Measurement of leptin at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of leptin during follow up | Measurement of leptin during follow up until the 48 months | 48 months | 
| Evaluation of catecholamines during follow up | Measurement of catecholamines during follow up until the 48 months | 48 months | 
| Evaluation of catecholamines during lifestyle intervention | Measurement of catecholamines at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of cortisol during lifestyle intervention | Measurement of cortisol at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of cortisol during follow up | Measurement of cortisol during follow up until the 48 months | 48 months | 
| Evaluation of glucagon-like peptide 1 (GLP1) during lifestyle intervention | Measurement of GLP1 at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of GLP1 during follow up | Measurement of GLP1 during follow up until the 48 months | 48 months | 
| Evaluation of glucose-dependent insulinotropic polypeptide (GIP) during lifestyle intervention | Measurement of GIP at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of GIP during follow up | Measurement of GIP during follow up until the 48 months | 48 months | 
| Evaluation of thyroid hormones during lifestyle intervention | Measurement of thyroid hormones at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of thyroid hormones during follow up | Measurement of thyroid hormones during follow up until the 48 months | 48 months | 
| Evaluation of insulin during lifestyle intervention | Measurement of insulin at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of insulin during follow up | Measurement of insulin during follow up until the 48 months | 48 months | 
| Evaluation of insulin-like growth factor 1 (IGF1) during lifestyle intervention | Measurement of IGF1 at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of IGF1 during follow up | Measurement of IGF1 during follow up until the 48 months | 48 months | 
| Evaluation of natriuretic peptide during lifestyle intervention | Measurement of natriuretic peptide at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up | month -3, month 0, month 12, month 18 | 
| Evaluation of natriuretic peptide during follow up | Measurement of natriuretic peptide during follow up until the 48 months | 48 months | 
| Evaluation of blood pressure during lifestyle intervention | Measurement of blood pressure at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 
| Evaluation of free fatty acids (FFAs) during lifestyle intervention | Measurement of FFAs at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 
| Evaluation of respiratory coefficient during lifestyle intervention | Measurement of respiratory coefficient at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 
| Measurement of messenger ribonucleic acid (mRNA) changes in adipose and skeletal muscle before (T-3), after weight loss (T0) and after as well as after 12 months randomized lifestyle intervention (or placebo) | Measurement of systemic and tissue specific changes in adipose tissue and skeletal muscle using RNA sequencing (counts) | month -3, month 0, month 12 | 
| Measurement of insulin sensitivity | Measurement of systemic and tissue specific changes in adipose and muscle insulin sensitivity using hyperinsulinemic clamp (mg•kg-1•min-1/(mU•L-1)) before (T-3), after weight loss (T0) and after as well as after 12 months randomized lifestyle intervention (or placebo) | month -3, month 0, month 12 | 
| Prediction of body weight regain | No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on long-term course of BMI (18 and 48 months) using mathematical models | month 18, month 48 | 
| Prediction of insulin sensitivity | No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on insulin sensitivity (18 and 48 months) using mathematical models | month 18, month 48 | 
| Prediction of energy expenditure | No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on energy expenditure (18 and 48 months) using mathematical models | month 18, month 48 | 
| Prediction of muscle mass | No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on muscle mass (18 and 48 months) using mathematical models | month 18, month 48 | 
| Prediction of fat mass | No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on fat mass (18 and 48 months) using mathematical models | month 18, month 48 | 
| BMI course after a lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo | BMI (kg/m2) after the randomized control trial (RCT) (18 months) will be analyzed up to 48 months. | month 24, month 36, month 48 | 
| changes of fatty acids during the intervention | Analysis of fatty acids at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 
| changes acylcarnitines | Analysis of acylcarnitines at baseline and after 3 months of weight loss | month -3, month 0 | 
| changes acylcarnitines | Analysis of acylcarnitines after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up | month 12, month 18, month 24, month 36, month 48 | 
| body composition | Whole body fat mass (kg, %) will be measured at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight regain, endocrine counterregulation