Clinical trial NCT05313594: Digital Twin - Modelling Postprandial Triglyceride and Glucose Responses
Official title: Digital Twin - Modelling Postprandial Triglyceride and Glucose Responses
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lipid Metabolism
Glucose Metabolism
Keywords: postprandial
lipids
glucose
dried blood spot
prediction model
metabolic responses
Lead sponsor: Wageningen University and Research
Sponsor class: OTHER
First posted: 2022-04-06
Enrollment: 38
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The population of the study will consist of generally healthy males and females aged 45-75, with a BMI ranging from 25 to 35 kg/m2. For this study, we will include 38 research subjects (aiming at 50% females).

Brief summary: Giving personalised dietary advice will help mitigate the postprandial increases in TG and glucose levels, and will assist in the battle against the increase in nutrition-related diseases, such as cardiovascular diseases. Being able to predict postprandial responses, will be a first step to personalised dietary advice.

The primary objective of this study is to validate the prediction model on the effect of a standardized mixed meal challenge on postprandial TG levels in a heterogenous group of middle-aged, overweight to obese individuals. The secondary objectives are 1) to improve the accuracy of the predicted postprandial TG responses by increasing the number of postprandial TG measurements, 2) to determine which parameters can improve the accuracy of the predicted postprandial TG responses, 3) to determine if we can predict the effect of a standardized mixed meal challenge on postprandial glucose levels in a heterogenous group of middle-aged, overweight to obese individuals, and 4) to determine which parameters can improve the accuracy of the predicted postprandial glucose responses. Another objective is to validate dried blood spots postprandial triglyceride concentrations against venous blood concentrations.

There are minor risks for the research subjects of this study. Research subjects will invest approximately 13.5 hours in the study. They will visit the Wageningen University research facility three times and Hospital Gelderse Vallei once.

Detailed description: Elevated triglyceride (TG) and glucose levels are major risk factors for cardiovascular diseases. Therefore, mitigating the postprandial increase in TG and glucose levels may help curb a person's risk of developing cardiovascular diseases. Current strategies to stimulate people to adopt a healthy lifestyle, however, are still insufficient. This is partly due to the fact that nutritional advice is nowadays still given at the population level via general nutrition guidelines, while nutritionist have long been aware that what works for one person may not work for another. Giving personalised dietary advice will help mitigate the postprandial increases in TG and glucose levels, and will assist in the battle against the increase in nutrition-related diseases, such as cardiovascular diseases. Being able to predict postprandial responses, will be a first step to personalised dietary advice.

The primary objective of this study is to validate the prediction model on the effect of a standardized mixed meal challenge on postprandial TG levels in a heterogenous group of middle-aged, overweight to obese individuals. The secondary objectives are 1) to improve the accuracy of the predicted postprandial TG responses by increasing the number of postprandial TG measurements, 2) to determine which parameters can improve the accuracy of the predicted postprandial TG responses, 3) to determine if we can predict the effect of a standardized mixed meal challenge on postprandial glucose levels in a heterogenous group of middle-aged, overweight to obese individuals, and 4) to determine which parameters can improve the accuracy of the predicted postprandial glucose responses. Another objective is to validate dried blood spots postprandial triglyceride concentrations against venous blood concentrations.

Digital twin is an observational study with three visits, including one mixed meal challenge test day.

Study population consists of 38 volunteers, 45-75 year old, BMI between 25-35 kg/m2.

The primary study parameter is the postprandial triglyceride responses in blood upon a mixed meal challenge. The secondary study parameters are: postprandial responses in the blood upon a mixed meal challenge, and extensive phenotyping of the subjects by collecting data on fasting blood profiles of micronutrients, metabolites, and proteins, continuous blood glucose levels (Freestyle Libre), body fat composition (DEXA), liver fat percentage (MRI), habitual dietary intake (FFQ), and physical activity (ActivPAL3).

This study is related to a broad general population. There are minor risks for the research subjects of this study. Consumption of the liquid mixed meal may cause some gastro-intestinal discomfort. Blood sampling will be performed via a cannula and the insertion can be a bit painful and may cause a bruise. The amount of blood that is drawn from subjects is within acceptable limits (total amount collected = 186mL). The radiation dose received during the DEXA scan for measuring body composition, is negligible compared to the average dose each person in the Netherlands receives per year. Research subjects will invest approximately 13.5 hours in the study. They will visit the Wageningen University research facility three times: once for a short screening, once to collect phenotyping data, and once for a mixed-meal challenge test day. In addition, they will visit Hospital Gelderse Vallei once for an MRI measurement.

Eligibility criteria: Inclusion Criteria:

* Male or female
* Age 45-75 y
* BMI 25-35 kg/m2
* Suitable veins for insertion of cannula

Exclusion Criteria:

* Having a gastro-intestinal disease, such as celiac disease, Crohn's disease, or Ulcerative colitis
* Having a history of intestinal surgery that might interfere with study outcomes, as determined by the medical supervisor. This does not include an appendectomy or cholecystectomy
* Presence of significant systemic diseases, such as diabetes mellitus, cancer, cardiovascular disease or respiratory disease, as determined by the medical supervisor
* Use of medications known to interfere with glucose or lipid homeostasis (e.g. corticosteroids, cholesterol-lowering medication, insulin, metformin), as determined by medical supervisor
* Blood clotting disorders
* Unstable body weight (weight gain or loss \>3 kg in the past three months)
* Reported slimming, medically prescribed or other extreme diets
* Alcohol consumption \>21 glasses a week
* Anaemia (Hb values \<7.5 mmol/L for women and \<8.5 mmol/L for men; checked at screening)
* Pregnant, lactating or wishing to become pregnant in the period of the study (self-reported)
* Having a pacemaker, implantable cardioverter-defibrillator, hearing implant, internal insulin pump, neurostimulator, aneurysm clips placed before 1990, or metal splinter in the eye
* Having claustrophobia
* Not willing to give up blood donation during the study
* Food allergies or intolerances for products that we use in the study
* Unwilling to consume non-vegan test meal
* Recent use of antibiotics (\<3 months prior to study start)
* Current smokers
* Abuse of soft and/or hard drugs
* Participation in another clinical trial at the same time
* Being an employee of the Food, Health \& Consumer Research group of Wageningen Food \& Biobased Research or Human Nutrition and Health Department of Wageningen University

Primary outcomes:
measure: Postprandial triglycerides blood levels
timeFrame: Baseline
measure: Postprandial triglycerides blood levels
timeFrame: 15 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 30 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 45 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 60 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 90 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 120 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 150 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 180 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 210 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 240 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 270 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 300 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 330 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 360 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 390 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 420 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 450 minutes post-ingestion
measure: Postprandial triglycerides blood levels
timeFrame: 480 minutes post-ingestion
Secondary outcomes:
measure: Postprandial glucose blood levels
timeFrame: Baseline
measure: Postprandial glucose blood levels
timeFrame: 15 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 30 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 45 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 60 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 90 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 120 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 150 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 180 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 210 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 240 minutes post-ingestion
measure: Postprandial glucose blood levels
timeFrame: 480 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: Baseline
measure: Postprandial insulin blood levels
timeFrame: 15 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 30 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 60 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 90 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 120 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 150 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 180 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 210 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 240 minutes post-ingestion
measure: Postprandial insulin blood levels
timeFrame: 480 minutes post-ingestion
Other outcomes:
measure: Blood glucose profile
timeFrame: Continuous for 5 days
measure: Physical activity
timeFrame: Continuous for 5 days
measure: Anthropometrics
timeFrame: Baseline
measure: Body composition
timeFrame: Baseline
measure: Habitual dietary intake
timeFrame: Baseline
measure: Liver fat
timeFrame: Baseline
measure: Micronutrient levels in blood
timeFrame: Baseline
measure: Metabolite levels in blood (full profile)
timeFrame: Baseline
measure: Protein levels in blood (full profile)
timeFrame: Baseline
measure: Triglyceride blood levels
timeFrame: Baseline
measure: Triglyceride blood levels
timeFrame: 120 minutes post-ingestion
measure: Triglyceride blood levels
timeFrame: 240 minutes post-ingestion
measure: Triglyceride blood levels
timeFrame: 480 minutes post-ingestion
Locations:
city: Wageningen
country: Netherlands
facility: Stichting Wageningen Research
state: Gelderland
Study officials:
affiliation: Wageningen University & Research
name: Diederik J Esser, PhD
role: PRINCIPAL_INVESTIGATOR
References: