Effects of Negative Energy Balance on Muscle Mass Regulation

Study Overview
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Brief Summary
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The investigators here propose to perform a prospective randomized intervention trial in post-menopausal women to investigate the endocrine network, which contributes to the changes in skeletal muscle mass during weight loss.

Official Title
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Effects of Negative Energy Balance on Muscle Mass Regulation

Conditions
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Weight Loss, Obesity, Skeletal Muscle, Insulin Sensitivity/Resistance

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) postmenopausal state Exclusion criteria: weight loss of more than 5kg in the last 2 months x unhealthy patients with: severe chronic diseases including cancer within the last 5 years, severe heart disease, severe impairment of hepatic or renal function, severe anaemia or disturbed coagulation eating disorders or any other psychiatric condition that would interact with the trial intervention malabsorption acute or chronic infections severe hypertension myopathy food allergies any other uncontrolled endocrine disorder changes of smoking habits, diets or medication that strongly affects energy homeostasis within the last 3 months prior to study inclusion

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Active Comparator: lifestyle intervention<br>Multimodal lifestyle intervention to reduce body weight | Behavioral: multimodal lifestyle intervention<br>* multimodal lifestyle intervention will be performed to reduce body weight<br>|
| Placebo Comparator: placebo<br>placebo | Behavioral: placebo<br>* no intervention, only follow up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of myocellular insulin sensitivity (hyperinsulinemic clamp) during negative energy balance and during stabilized modification of body composition after weight loss. | Analysis of myocellular insulin sensitivity by hyperinsulinemic clamp in mg•kg-1•min-1/(mU•L-1) | 4 months | 
| Changes of skeletal muscle mass (air displacement plethysmography) during negative energy balance and during stabilized modification of body composition after weight loss. | Analysis of muscle mass (in % of body weight) | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects on energy expenditure | Measurement of energy expenditure (kcal/d), postprandial thermogenesis (%) and respiratory coefficient | 4 months | 
| Effects on myocellular and adipose tissue metabolism and substrate utilization | Measurement of myocellular and adipose metabolism using microdialysis (glycerol (µmol/l), lactate (mmol/l), pyruvate (µmol/l), glucose (mmol/l)) during oral glucose load (180 minutes) | 4 months | 
| Effects on myocellular and adipose tissue mRNA expression | Analysis of myocellular and adipose mRNA expression (RNA sequencing) in counts | 4 months | 
| Weight regain | Analysis of body weight regain (BMI; kg/m2) during follow up | 24 months | 
| Fat mass | Analysis of body fat (kg and %) | 24 months | 
| Measurement of human gut microbiome at baseline, during weight loos, after weight loss (negative energy balance) and during stabilized modification of body composition 4 weeks after weight loss | 16S rRNA sequencing and/or shotgun metagenomic pyrosequencing of the gut microbiota for assessment of microbiota composition and gene abundances. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight loss, muscle mass