DAILICATE: Dairy Lipids and Cardiometabolic Risk

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05783466

Collaborator

Laboratoire de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition (CarMen) (Other), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA) (Other), Institut national de la recherche agronomique (INRAE U.1397) (Other)

Enrollment

Locations

Arms

28.1

Anticipated Duration (Months)

37.5

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Morbid Obesity	Other: Low-fat dairy products Other: Whole-fat dairy products Other: Milk polar lipid enriched whole-fat dairy products	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Bioactive Dairy Lipids to Manage Cardiometabolic Risk in Obesity

Anticipated Study Start Date :

May 2, 2023

Anticipated Primary Completion Date :

Sep 2, 2025

Anticipated Study Completion Date :

Sep 2, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Low-fat dairy products within a dietary handling for weight loss 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 3-month intervention
Experimental: Whole-fat dairy products within a dietary handling for weight loss 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 3-month intervention
Experimental: Whole-fat dairy products enriched with milk polar lipids within a dietary handling for weight loss 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 3-month intervention

Arm

Intervention/Treatment

Other: Low-fat dairy products within a dietary handling for weight loss

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

3-month intervention

Experimental: Whole-fat dairy products within a dietary handling for weight loss

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

3-month intervention

Experimental: Whole-fat dairy products enriched with milk polar lipids within a dietary handling for weight loss

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

3-month intervention

Outcome Measures

Primary Outcome Measures

Total plasma apolipoprotein B concentration [day 0 and day 90]
Change in fasting total plasma apolipoprotein B concentration after 3-month intervention, measured by ELISA.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women between 18-50 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre de Recherche en Nutrition Humaine Rhône-Alpes	Pierre-Bénite		France	69310
2	Centres Hospitalier Lyon Sud, Service d'Endocrinologie-Diabète-Nutrition	Pierre-Bénite		France	69310

Sponsors and Collaborators

Hospices Civils de Lyon
Laboratoire de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition (CarMen)
Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA)
Institut national de la recherche agronomique (INRAE U.1397)