Lifestyle Intervention on Metabolic Homeostasis

Study Overview
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Brief Summary
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This is an exploratory controlled before-after study, which involves 112 participants, of whom 28 are with normal weight and 84 are overweight or obese. Twelve weeks of personalized nutritional and lifestyle weight reduction intervention will be conducted in the overweight or obese participants. The objectives of this study are to 1) characterize metabolic homeostasis under resting and exercise conditions, 2) to explore the potential impact factors on metabolic homeostasis, and 3) to investigate whether personalized nutritional and lifestyle weight reduction intervention can improve metabolic health in overweight or obese Chinese individuals and how is it comparable to healthy normal weight Chinese population.

Detailed Description
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The objectives of this study are to 1) characterize metabolic homeostasis under resting and exercise conditions, 2) to explore the potential impact factors on metabolic homeostasis, and 3) to investigate whether personalized nutritional and lifestyle weight reduction intervention can improve metabolic health in overweight or obese Chinese individuals and how is it comparable to healthy normal weight Chinese population. In this study, 84 overweight or obese participants (BMI ≥ 24 kg/m2) and 28 normal weight participants (18.5 ≤ BMI<24 kg/m2) will be recruited and receive 12-week personalized weight reduction or weight maintenance nutritional and lifestyle interventions. Before and after the 12-week interventions, metabolic homeostasis will be used to characterize metabolic health and to be determined using comprehensive measurements of dynamic changes in postprandial metabolic responses (including energy metabolism, multiple clinical biomarkers, metabolomic signatures, gut microbiota, genetic signatures etc.) after the standardized mixed-nutrient dietary challenges (75 g glucose, 60 g fat and 20 g protein) in whole room indirect calorimeter under both resting and exercise conditions. In addition, data from dietary intake, anthropometric measurements, body composition, psychosocial measures, behavior questionnaires and 14-day continuous glucose monitoring will also be collected to characterize metabolic homeostasis. During the interventions, participants will receive personalized dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. APP-connected wearable devices will be utilized to monitor their dietary intakes, physical activities and sleep conditions, and an application-connected scale will be used to monitor their weight changes during interventions. The study's protocol has been approved by the Ethics Committee of Sir Run Run Shaw Hospital.

Official Title
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Exploratory Personalized Lifestyle Intervention on Metabolic Homeostasis in Overweight or Obese Chinese Population

Conditions
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Homeostasis, Metabolism and Nutrition Disorder, Healthy, Obesity

Intervention / Treatment
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* Behavioral: General lifestyle and nutritional education
* Behavioral: Personalized nutritional and lifestyle weight reduction intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20-70 years of age, inclusive BMI ≥ 24kg/m2 Not in other clinical studies currently or in the past three months Exclusion Criteria: Fasting glucose >7.0mmol/L or diagnosed diabetes or taking insulin or other blood glucose-lowering drugs Blood pressure > 160/100 mmHg; diagnosed phase II or III hypertension or cannot decrease SBP under 160mmHg after anti-hypertension drugs Fasting blood TG≥ 5.7 mmol/L or fasting LDL-C≥ 4.9 mmol/L or cannot control TG < 5.7 mmol/L or LDL-C < 4.9 mmol/L after taking lipid lowering drugs Pregnant or lactating Attempting to change body weight in the past 3 months Use of antibiotic in the preceding 3 months for 3-serial days Use of estrogen therapy or hormonal drugs in the preceding 6 months Smokers History of alcohol abuse or other substance abuse (Alcohol abuse is defined as regular alcohol consumption > 40 g/day for females or > 80 g/day for males) Severe renal disease or liver disease Severe gastrointestinal diseases Surgical events preceding 1 year (except appendicitis or hernia surgery) Severe cardiovascular or cerebrovascular diseases Implantation of heart stent or any device containing metal material Cancer or receiving radiotherapy and chemotherapy within 5 years Hyperthyroidism or hypothyroidism Suffering from AIDS, hepatitis A, hepatitis B and other infectious diseases Claustrophobia Physical disability Any mental disorders or current use of antidepressants Cognitive disability

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Healthy Comparators<br>They will receive general lifestyle and nutritional education. | Behavioral: General lifestyle and nutritional education<br>* Participants will receive general dietary advice, behavior guidance and nutritional and lifestyle education based on dietary guidelines.<br>|
| Experimental: Overweight/Obese Group<br>They will receive personalized nutritional and lifestyle weight reduction intervention including dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. | Behavioral: Personalized nutritional and lifestyle weight reduction intervention<br>* Participants will receive personalized dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. APP-connected wearable devices will be utilized to monitor their dietary intakes, physical activities and sleep conditions and APP-connected scale will be used to monitor their weight changes during interventions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Metabolic Homeostasis Score at 12 Weeks | A metabolic homeostasis score is a composite score that includes aggregated changes in blood biomarkers (metabolites or biomarkers or index involved in carbohydrates metabolism such as glucose, C-peptide, Matsuda index etc.; metabolites or biomarkers involved in lipid metabolism such as high-density lipoprotein cholesterol, total cholesterol, triglyceride etc.; metabolites or biomarkers involved in protein/vitamin metabolism such as creatinine; inflammatory or cytokines such as interleukin-6 etc.; hormones; anthropometric measures etc.). The metabolic homeostasis score is a composite score, that is calculated by the average of the scores of above-mentioned features using a certain computational algorithm. The larger the metabolic homeostasis score is, the worse the homeostatic resilience of the person, and vice versa. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Body Weight at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Weight will be assessed by Seca-255 (ScalesGalore). | Baseline and Week 12 | 
| Change from Baseline in Body Mass Index at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Weight and height will be assessed by Seca-255 (ScalesGalore). | Baseline and Week 12 | 
| Change from Baseline in Waist Circumference at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Waist circumference will be assessed by Seca-201(ScalesGalore). | Baseline and Week 12 | 
| Change from Baseline in Hip Circumference at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Waist circumference will be assessed by Seca-201(ScalesGalore). | Baseline and Week 12 | 
| Change from Baseline in Blood Pressure at 12 Weeks | The change of systolic and diastolic blood pressures between the baseline and after 12-week lifestyle intervention. Both systolic pressure and diastolic pressure will be assessed using electronic blood pressure monitor (Omron J750). | Baseline and Week 12 | 
| Change from Baseline in Heart Rate at 12 Weeks | The change of systolic and diastolic blood pressures between the baseline and after 12-week lifestyle intervention. Heart rate will be assessed using Omron J750. | Baseline and Week 12 | 
| Change from Baseline in Body Composition at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Body composition will assessed using dual energy x-ray absorptiometry (DXA) (GE). | Baseline and Week 12 | 
| Change from Baseline in Energy Expenditure at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Energy expenditure will be assessed using whole room indirect calorimeter. | Baseline and Week 12 | 
| Change from Baseline in Respiratory Quotient at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Respiratory quotient will be assessed using whole room indirect calorimeter. | Baseline and Week 12 | 
| Change from Baseline in Glucose Homeostasis at 12 Weeks | The change between the baseline and after 12-week lifestyle intervention. Glucose homeostasis will be assessed by Continuous Glucose Monitoring (FreeStyle Libre). | Baseline and Week 12 | 
| Change from Baseline in Glucose at 12 Weeks | The dynamic change of glucose from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in C-peptide at 12 Weeks | The dynamic change of C-peptide from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Insulin Indices at 12 Weeks | The dynamic change of insulin indices from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Lipid Parameters at 12 Weeks | The dynamic change of lipid parameters from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Protein and Amino Acids Metabolites at 12 Weeks | The dynamic change from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Inflammatory Biomarkers and Cytokines at 12 Weeks | The dynamic change from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Gastrointestinal Hormones at 12 Weeks | The dynamic change in gastrointestinal hormones from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Cell Adhesion Molecules at 12 Weeks | The dynamic change in cell adhesion molecules from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Adipokines at 12 Weeks | The dynamic change in adipokines from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. | Baseline and Week 12 | 
| Change from Baseline in Metabolomics at 12 Weeks | The dynamic change in metabolomics including profiling of free fatty acids and other metabolites from 0 to 30, 60, 120, 180, 240, 300 minutes pre- and post-oral mixed-nutrient dietary challenge between the baseline and after 12-week lifestyle intervention. Metabolomics will be measured by LC-MS. | Baseline and Week 12 | 
| Single nucleotide polymorphism (SNPs) | Mutations at specific sites will be detected by gene chip. | Baseline | 
| Gut microbiota 16S rDNA sequencing | Gut microbiota 16S rDNA will be sequenced and community composition will be analyzed. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic homeostasis, Healthy, Lifestyle intervention