MERITS: The Effect of Whey Protein and Dietary Fibers on Risk Markers of the Metabolic Syndrome and Bone Health

Sponsor

Aarhus University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02931630

Collaborator

University of Aarhus (Other), Rigshospitalet, Denmark (Other), University of California, Davis (Other), University of Copenhagen (Other)

Enrollment

Location

Arms

13.9

Actual Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The prevalence of overweight and lifestyle related diseases such as cardiovascular disease (CVD) and type 2 diabetes (T2D) is increasing world wide. The metabolic syndrome (MeS) is a condition characterized by abdominal obesity, high blood lipids, high blood pressure and elevated blood sugar. MeS is associated with an increased risk of developing CVD and T2D. Dietary fibers and whey protein have independently shown beneficial effects on several of these risk factors in previous studies. Whey protein is furthermore seen to show positive effects on bone turnover.

The purpose of this trial is to investigate whether an increased intake of dietary fibers and whey protein (separately or combined) over a period of 12 weeks will affect the risk markers of MeS and bone turnover in abdominally obese subjects.

A total of 80 people with abdominal obesity will be included. The design is a randomized, double blinded, controlled dietary intervention trial. Subjects are assigned to one of four experimental groups. Each group are provided with test products containing either high or low whey protein and high or low dietary fibers to replace part of their regular diet. The subjects are instructed in how to incorporate the test products in their habitual diets in order to maintain weight stability.

The primary outcome is postprandial lipaemia (PPL) - an independent risk factor of developing CVD. PPL is estimated by performing a standardized high fat meal test during which postprandial level of triglycerides is measured. The authors hypothesize that a diet of high content of whey protein and high dietary fiber during 12 weeks will induce a reduction in PPL.

Condition or Disease	Intervention/Treatment	Phase
Abdominal Obesity Metabolic Syndrome Type 2 Diabetes Cardiovascular Disease	Other: Whey protein powder Other: Maltodextrin powder Other: High fiber bread Other: Low fiber bread	N/A

Detailed Description

Please refer to summary

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

The Effect of Whey Protein and Dietary Fibers on Risk Markers of the Metabolic Syndrome and Bone Health

Actual Study Start Date :

May 1, 2016

Actual Primary Completion Date :

Jun 29, 2017

Actual Study Completion Date :

Jun 29, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HP/HF Whey protein powder / High fiber bread	Other: Whey protein powder 60 g of whey protein powder Other: High fiber bread Wheat bread with high content of dietary fibers (approximately 30 g fibers/day)
Experimental: HP/LF Whey protein powder / Low fiber bread	Other: Maltodextrin powder 60 g of Maltodextrin powder Other: Low fiber bread Wheat bread with low content of dietary fibers (approximately 10 g fibers/day)
Experimental: LP/HF Maltodextrin powder / High fiber bread	Other: Maltodextrin powder 60 g of Maltodextrin powder Other: High fiber bread Wheat bread with high content of dietary fibers (approximately 30 g fibers/day)
Experimental: LP/LF Maltodextrin powder / Low fiber bread	Other: Whey protein powder 60 g of whey protein powder Other: Low fiber bread Wheat bread with low content of dietary fibers (approximately 10 g fibers/day)

Outcome Measures

Primary Outcome Measures

Postprandial triglyceride response [Meal test: -15, 0, 60, 90, 120, 240, 360 min. Performed at baseline and at 12 weeks.]
Postprandial triglyceride response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.

Secondary Outcome Measures

24 hours blood pressure (BP) [Performed at baseline and week 12]
Arteriograph 24, TensioMed, Hungary
24 hours augmentation Index (AI) [Performed at baseline and week 12]
Arteriograph 24, TensioMed, Hungary
Respiratory Exchange Ratio [Meal test: -30 and 140 min. Performed at baseline and week 12.]
Measured twice during each meal test by indirect calorimetry (hood)
Body composition [Performed at baseline and week 12]
Dual Energy X-ray Absorptiometry (DEXA) scan: Total body fat percentage, lean mass percentage, gynoid and android fat percentage
Postprandial apolipoprotein B48 response [Meal test: -15, 0, 60, 240, 360 min. Performed at baseline and at 12 weeks.]
Postprandial apolipoprotein response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.
Glucose response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
Glucose response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.
Insulin response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
Insulin response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.
Glucagon response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
Glukagon response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360 min) following a high-fat meal.
Glucagon-like peptide 1 (GLP-1) response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
GLP-1 response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360
Glucagon-like peptide 2 (GLP-2) response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
GLP-2 response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360
Glucose-dependent insulinotropic polypeptide (GIP) response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
GIP response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360
Ghrelin response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
Ghrelin response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360
Peptide tyrosine tyrosine (PYY) response during high-fat meal test [Meal test: -15, -10, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
PYY response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360
Adiponectin response during high-fat meal test [Meal test: -15, 0, 15, 30, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
Adiponectin response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360)
Non-esterified fatty acids (NEFA) response during high-fat meal test [Meal test: -15, 0, 60, 90, 120, 240, 360 min. Performed at baseline and week 12]
NEFA response measured as fasting value and incremental Area Under the Curve (iAUC from -15 - 360)
Interleukin-6 (IL-6) response during high-fat meal test [Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12]
IL-6 response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
Monocyte chemoattractant protein 1 (MCP-1) response during high-fat meal test [Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12]
MCP-1 response measured as fasting value and incremental Area Under the Curve (iAUC from 0 - 240 min)
RANTES (CCL5) response during high-fat meal test [Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12]
CCL5 response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
High-sensitive c-reactive protein (hs-CRP) response during high-fat meal test [Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12]
hs-CRP response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
Procollagen type 1 N-terminal propeptide (P1NP) response during high-fat meal test [Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12]
P1NP response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
C-telopeptide (CTX) response during high-fat meal test [Meal test: 0, 15, 30, 60, 90, 120, 240 min. Performed at baseline and week 12]
CTX response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
Parathyroid hormone (PTH) response during high-fat meal test [Meal test: 0, 15, 30, 90, 240 min. Performed at baseline and week 12]
PTH response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
Osteoprotegrin response during high-fat meal test [Meal test: 0, 15, 30, 90, 240 min. Performed at baseline and week 12]
Osteoprotegrin response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
Osteocalcin response during high-fat meal test [Meal test: 0, 15, 30, 90, 240 min. Performed at baseline and week 12]
Osteocalcin response measured as fasting value and incremental Area Under the Curve (iAUC from 0-240 min)
25-dihydroxy vitamin D [Change from week 0 to week 12]
Fasting value measured at baseline and week 12
Phosphate [Change from week 0 to week 12]
Fasting value measured at baseline and week 12
Magnesium [Change from week 0 to week 12]
Fasting value measured at baseline and week 12
Total cholesterol [Change from week 0 to week 12]
Fasting value measured at baseline and week 12
Low density lipoprotein (LDL) [Change from week 0 to week 12]
Fasting value measured at baseline and week 12
High density lipoprotein (HDL) [Change from week 0 to week 12]
Fasting value measured at baseline and week 12
Glucose response during oral glucose tolerance test (OGTT) [OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12]
Glucose measured as incremental Area Under the Curve (iAUC from -15 - 120 min)
Insulin response during oral glucose tolerance test (OGTT) [OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12]
Insulin measured as incremental Area Under the Curve (iAUC from -15 - 120 min)
Glucagon response during oral glucose tolerance test (OGTT) [OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12]
Glucagon measured as incremental Area Under the Curve (iAUC from -15 - 120 min)
Glucagon-like peptide 1 (GLP-1) response during oral glucose tolerance test (OGTT) [OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12]
GLP-1 measured as incremental Area Under the Curve (iAUC from -15 - 120 min)
Glucagon-like peptide 2 (GLP-2) response during oral glucose tolerance test (OGTT) [OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12]
GLP-2 measured as incremental Area Under the Curve (iAUC from -15 - 120 min)
Glucose-dependent insulinotropic polypeptide (GIP) response during oral glucose tolerance test (OGTT) [OGTT: -15, -10, 0, 30, 60, 90, 120 min. Performed at baseline and week 12]
GIP measured as incremental Area Under the Curve (iAUC from -15 - 120 min)
Parathyroid hormone (PTH) response during oral glucose tolerance test (OGTT) [OGTT: 0, 30, 90 min. Performed at baseline and week 12]
PTH measured as incremental Area Under the Curve (iAUC from 0-90 min)
C-telopeptide (CTX) response during oral glucose tolerance test (OGTT) [OGTT: 0, 30, 90 min. Performed at baseline and week 12]
CTX measured as incremental Area Under the Curve (iAUC from 0-90 min)
Procollagen type 1 N-terminal propeptide (P1NP) response during oral glucose tolerance test (OGTT) [OGTT: 0, 30, 90 min. Performed at baseline and week 12]
P1NP measured as incremental Area Under the Curve (iAUC from 0-90 min)
Osteoprotegrin response during oral glucose tolerance test (OGTT) [OGTT: 0, 30, 90 min. Performed at baseline and week 12]
Osteoprotegrin measured as incremental Area Under the Curve (iAUC from 0-90 min)
Osteocalcin response during oral glucose tolerance test (OGTT) [OGTT: 0, 30, 90 min. Performed at baseline and week 12]
Osteocalcin measured as incremental Area Under the Curve (iAUC from 0-90 min)
Waist and hip circumference. [Change from week 0 to week 12]
Waist and hip circumference in cm
Body weight [Change from week 0 to week 12]
Body weight in kg
Body Mass Index [Change from week 0 to week 12]
kg/m2
Adipose tissue gene expression [Change from week 0 to week 12]
Subcutaneous fat tissue biopsy performed at baseline and week 12 for the measurement of changes in genes related to lipid and glucose metabolism and insulin signalling.
Adipose tissue proliferation and differentiation [Change from week 0 to week 12]
Subcutaneous fat tissue biopsy performed at baseline and week 12 for measuring proliferation and differentiation processes of preadipocyte stem cells into mature adipocytes, and to test the effect of diets on expanding the capacity of the subcutaneous adipose tissue to store fat.
Urinary calcium [Change from week 0 to week 12]
Urinary calcium excretion measured in 24-hour urine samples collected at baseline and week 12
Urinary nitrogen [Change from week 0 to week 12]
Urinary nitrogen excretion measured in 24-hour urine samples collected at baseline and week 12
Metabolomics, plasma [OGTT: -15, 30, 60, 90, 120 min. Performed at baseline and week 12.]
Non-targeted metabolomics analysis using Liquid Chromatography - Mass Spectrometry
Metabolomics, urine [24-hour urine collection performed at baseline and week 12.]
Non-targeted metabolomics analysis using Liquid Chromatography - Mass Spectrometry
Metabolomics, faeces [Collected at baseline and week 12.]
Non-targeted metabolomics analysis using Liquid Chromatography - Mass Spectrometry
Insulin sensitivity during oral glucose tolerance test (OGTT) [OGTT performed at baseline and week 12 (blood sampling at -15, -10, 0, 30, 60, 90, 120 min)]
Homeostasis model assessment - insulin resistance (HOMA-IR) and Matsuda Index calculated based on blood glucose and insulin measurements during OGTT
Appetite assessment during high-fat meal test [Meal test: Questionnaire at -10, 0, 30, 60, 90, 120, 180, 240, 300, 360 min. Performed at baseline and week 12.]
Visual Analog Scale (VAS) electronic questionnaire
Microbiota [Faecal samples collected at baseline and week 12.]
Non-targeted microbiome and metabolome analyses using high-throughput DNA sequencing on Illumina Miseq and Liquid Chromatography - Mass Spectrometry (LC-MS) metabolomics,

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Waist circumference ≥ 80 cm (women)/94 cm (men)
Age ≥40 years

Exclusion Criteria:

Significant cardiovascular, renal or endocrine disease
History of diabetes
≥ 3 kg of weight gain or loss within the last 3 months
Any change in medication within the last month
Treatment with steroids
Pregnancy, breastfeeding or planned pregnancy
Psychiatric history
Alcohol or drug addiction
Dietary fiber supplement within the last month

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aarhus University Hospital, Dep. of clinical nutrition research	Aarhus		Denmark	8000

Sponsors and Collaborators

Aarhus University Hospital
University of Aarhus
Rigshospitalet, Denmark
University of California, Davis
University of Copenhagen

Investigators

Principal Investigator: Søren Gregersen, MD, ph.d., Aarhus University Hospital
Study Chair: Knud Erik B. Knudsen, Professor, Department of Animal Science, University of Aarhus