Dairy Lipids and Cardiometabolic Risk

Study Overview
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Brief Summary
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It is a randomized parallel arm intervention study in adults with severe obesity. The objective is to demonstrate that within a dietary handling for weight loss, the daily ingestion during 3 months of whole dairy products enriched with milk polar lipids or whole dairy products decreases to a greater extent fasting plasma apolipoprotein B concentrations than the daily ingestion of low-fat dairy products (control group). Metabolic parameters will be assessed before and after the 3-month intervention, both at fasting and in postprandial period after the consumption of standardized meals.

Official Title
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Bioactive Dairy Lipids to Manage Cardiometabolic Risk in Obesity

Conditions
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Morbid Obesity

Intervention / Treatment
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* Other: Low-fat dairy products
* Other: Whole-fat dairy products
* Other: Milk polar lipid enriched whole-fat dairy products


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between 18-70 years Body Mass Index (BMI) between 40 and 55 kg/m2 inclusive Stable body weight (weight change +/- 5 % for 3 months prior to screening) Consumption of at least 1 serving/day of dairy products made from cow's milk Informed consent Exclusion Criteria: History of bariatric or digestive surgery or disease interfering with main outcomes Drinking more than 3 glasses of alcohol per day (>30g/day) Pregnancy, parturiency or breastfeeding Food allergies or intolerance to dairy products Dietary restriction (vegetarian or lactovegetarian) or high protein diet Use of dietary supplements Treated with lipid lowering drugs (fibrates, statins, anti-PCSK9, ezetimibe, cholestyramine) within the last 6 weeks before study entry Treated with insulin, GLP-1 analogs, acarbose, corticoids, beta-blockers. Medications interfering with intestinal microbiota (beta-lactamines within 3 months before the study or laxatives) Smoking ≥ 5 cigarettes/day during the past 6 months.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low-fat dairy products within a dietary handling for weight loss<br>3 servings/day of low-fat dairy products: 1 serving of low-fat cheese, 1 serving of low-fat yogurt and 1 serving of (semi-)skimmed milk. | Other: Low-fat dairy products<br>* 3-month intervention<br>|
| Experimental: Whole-fat dairy products within a dietary handling for weight loss<br>3 servings/day of whole-fat dairy products: 1 serving of whole cheese, 1 serving of whole yogurt and 1 serving of whole milk. | Other: Whole-fat dairy products<br>* 3-month intervention<br>|
| Experimental: Whole-fat dairy products enriched with milk polar lipids within a dietary handling for weight loss<br>3 servings/day of whole-fat dairy products (1 milk, 1 yogurt, 1 cheese) among which 1 serving/day is enriched with milk polar lipids via butterier. | Other: Milk polar lipid enriched whole-fat dairy products<br>* 3-month intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total plasma apolipoprotein B concentration | Change in fasting total plasma apolipoprotein B concentration after 3-month intervention, measured by ELISA. | day 0 and day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in weight | Changes in weight after 3-month intervention. | day 0 and day 90 | 
| Anthropometric measurements 2 | Changes in waist and hip circumferences after 3-month intervention. | day 0 and day 90 | 
| Body mass composition measurements | Change in body mass composition (lean mass, fat mass) after 3-month intervention, analyzed by impedancemeter | day 0 and day 90 | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods | Changes in plasma concentrations of triglycerides | day 0 and day 90 for fasting and postprandial measurements. • For postprandial measurements: times 60 minutes-120 minutes -180 minutes -240 minutes -270 minutes -300 minutes -360 minutes | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 2 | Changes in plasma concentrations of total cholesterol | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: times 120 minutes -180 minutes -240 minutes -270 minutes -300 minutes. | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 3 | Changes in plasma concentrations of LDL-cholesterol | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: time 360 minutes. | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 4 | Changes in plasma concentrations of HDL-cholesterol | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: time 360 minutes. | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 5 | Changes in plasma concentrations of apoB100 | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: times 120 minutes -240 minutes -300 minutes. | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 6 | Changes in plasma concentrations of apoB48 | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: times 120 minutes -240 minutes -300 minutes - 360 minutes | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 7 | Changes in plasma concentrations of apoA1 | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements:times 360 minutes. | 
| Plasma lipid concentrations after 3-month intervention, measured using standard laboratory methods 8 | Changes in plasma concentrations of unesterified fatty acids | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: times 120 minutes -240 minutes | 
| Glucose concentrations after 3-month intervention, measured using standard laboratory methods | Changes in plasma concentrations of glucose | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: times 120 minutes -240 minutes | 
| Glucose concentrations after 3-month intervention, measured using standard laboratory methods 2 | Changes in plasma concentrations of insulin | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements: times 120 minutes -240 minutes | 
| Targeted plasma lipidomics after 3-month intervention | Changes in plasma concentrations of phospholipids | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted plasma lipidomics after 3-month intervention 2 | Changes in plasma concentrations of sphingolipids (sphingomyelins and ceramides) | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted plasma lipidomics after 3-month intervention 3 | Changes in plasma concentrations of lysophospholipids | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted plasma lipidomics after 3-month intervention 4 | Changes in plasma concentrations of fatty acids in plasma total lipids | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted plasma lipidomics after 3-month intervention 5 | Changes in plasma concentrations of phospholipids | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted chylomicrons of plasma after 3-month intervention | Changes in concentrations of triglycerides | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted chylomicrons of plasma after 3-month intervention 2 | Changes in concentrations of cholesterol | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted chylomicrons of plasma after 3-month intervention 3 | Changes in concentrations of sphingolipids | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Targeted chylomicrons of plasma after 3-month intervention 4 | Changes in concentrations of fatty acids | day 0 and day 90 for fasting and postprandial measurements For postprandial measurements :times 120 minutes -240 minutes -300 minutes -360 minutes. | 
| Inflammation markers | Changes in adiponectin | day 0 and day 90 for fasting and postprandial measurements. | 
| Inflammation markers 2 | Changes in CRP | day 0 and day 90 for fasting and postprandial measurements. | 
| Inflammation markers 3 | Changes in cytokines | day 0 and day 90 for fasting and postprandial measurements. | 
| Inflammation markers 4 | Changes in LBP | day 0 and day 90 for fasting and postprandial measurements. | 
| Inflammation markers 5 | Changes in endotoxins | day 0 and day 90 for fasting and postprandial measurements. | 
| Inflammation markers 6 | Changes in CD14 | day 0 and day 90 for fasting and postprandial measurements. | 
| Inflammation markers 7 | Gene expressions of inflammation markers after 3-month intervention, measured with dedicated kits and PAXgene kit | day 0 and day 90 for fasting and postprandial measurements. | 
| Platelet activation markers | Changes in thromboxane B2 concentrations in platelets (from blood donors) stimulated by lipoproteins (chylomicrons and HDL) after 3-month intervention, measured with an ELISA kit. Differences in the percents of aggregation of platelets incubated with lipoproteins (chylomicrons and HDL) after 3-month intervention, assessed by light transmission aggregometry. | day 0 and day 90 for fasting and postprandial measurements. For postprandial measurements,times 120 minutes-240 minutes-300 minutes -360 minutes. | 
| Oxidative stress marker | Changes in urinary concentrations of 8-iso-PGF2 alpha isoprostane after 3-month intervention, determined with an ELISA kit | day 0 and day 90 | 
| Markers of immune cells | PBMC | day 0 and day 90 | 
| Markers of immune cells 2 | Complete blood counts | day 0 and day 90 | 
| Intestinal microbiota after 3-month intervention. | Changes in microbiome composition and diversity (alpha, beta) of feces (16S analysis) | day 0 and day 90 | 
| Intestinal microbiota after 3-month intervention 2 | Changes in fecal concentrations of microbiota-derived metabolites (coprostanol, short chain fatty acids (SCFA), calprotectin) | day 0 and day 90 | 
| Questionnaires on physical activity | International Physical Activity Questionnaire ([i] ëinactive, [ii] ëminimally active, [iii] ëHEPA activeí (health enhancing physical activity; a high active category).) | day 0 and day 90 | 
| Questionnaires on digestive comfort | Liker scale | day 0 and day 90 | 
| Questionnaires on digestive comfort | Bristol stool scale | day 0 and day 90 | 
| Questionnaires on product satiety | Satiety from visual analog scale (VAS) | day 0 and day 90 | 
| Questionnaires food intake | Three-factor eating questionnaire (TFEQ) | day 0 and day 90 | 
| Questionnaires on product appreciation | Product appreciation questionnaire | day 0 and day 90 | 
| Dietary intake questionnaire | Dietary record questionnaire | day 0 and day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Nutrition, Dietary intervention, Weight loss, Metabolism, Dairy, Fat, Milk polar lipids