Clinical trial NCT06923644: Targeted Precision Nutrition Strategy To Prevent Chronic Metabolic Diseases
Official title: Targeted Precision Nutrition Strategy To Prevent Chronic Metabolic Diseases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Obesity and Overweight
Pre-diabetic
Type 2 Diabetes Mellitus (T2DM)
Keywords: Dietary intervention trial
Precision nutrition
Tissue-specific insulin resistance
Body composition
Metabotyping
Glucose homeostasis
Cardiometabolic health
Insulin resistance
Metabolic phenotype
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Wageningen University and Research
name: Health Holland
name: TKI Agri & Food
name: Nestle Health Science
name: Beneo GmbH
name: BARILLA G. e R. Fratelli S.p.A., Parma, Italy
First posted: 2025-04-11
Enrollment: 240
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Nutrition is very important to keep blood sugar levels balanced. If blood sugar levels are too high, it can lead to diseases such as cardiovascular disease and type 2 diabetes (T2DM). Therefore, adjusting what one eats, also called a diet or nutritional intervention, can help prevent these diseases. However, not everyone responds the same to a diet. In about 30% of people, a diet does not work as hoped. This can be due to various reasons, such as a person's metabolism, genetic predisposition, the composition of the food one eats, or the bacteria in the intestines. Everyday things like sleep, stress, and movement also play a role. The investigators used a computer model to classify people with overweight and obesity into groups based on these factors. The investigators call such a group a 'Metabolic Phenotype', or in short 'Metabotype'. Based on the Metabotype, a personalised diet was developed (personalised nutrition intervention) that may better suit each person's unique situation.

The investigators hypothesize that a precision nutrition intervention, tailored to Metabotypes identified through unsupervised clustering (using the aforementioned computer model) of predefined, accurate features related to cardiometabolic health-specifically, tissue-specific glucose and lipid metabolism and detailed body composition-will enhance blood glucose homeostasis, reduce cardiometabolic risk, and improve adherence to the intervention and mental well-being, compared to population-based dietary guidelines. The present project will contribute to targeted and efficient precision-based dietary strategies for individuals at increased risk of T2DM.

Detailed description: Objective:

Our study aims to identify unique Metabotypes among individuals with overweight and obesity and assess their response to a 1-year precision dietary macronutrient modulation. The objective is to provide proof-of-concept that this approach improves glucose homeostasis, dietary adherence, and psychosocial well-being compared to population-based dietary guidelines.

Study design:

Two-centre dietary intervention study with a double-blind, randomised controlled parallel design, based on participants' Metabotype and hypothesized optimal diet. Participants' Metabotype and intervention arm will be blinded to the participants and researchers. Metabotypes were identified through hierarchical clustering of Principal Components (HCPC) using baseline data from The Maastricht Study (participant demographics, body composition, glucose- and insulin metabolism), whereafter clusters were cross-validated in independent cohorts. Based on a combination of post-hoc analyses of dietary intervention trials and literature, the optimal dietary macronutrient composition was determined for these Metabotypes.

Study population:

In total 240 men and women with overweight and obesity (age 40-75 years, BMI 25-40 kg/m2) will be included. Further details on in- and exclusion criteria will be described under ''Eligibility''. Following screening and baseline measurements, for each eligible participant, a classification algorithm will determine the participants' Metabotype cluster (one of three possible Metabotypes for each sex).

Intervention:

Following screening, baseline measurements, and determination of Metabotype, participants will be randomly assigned, using minimization, to either the Precision Nutrition (PN) group or the Control (CN) group. The PN group will receive a hypothesized optimal diet for their specific Metabotype, while the control group will be randomly assigned one of the diets optimized for a different Metabotype of the same sex. All participants will follow their assigned diets for 12 months, with each diet conforming to the Dutch healthy dietary guidelines. Participants will receive regular dietary consultation, and meal plans including variation lists to guide them with their dietary intake during the intervention.

Main study parameters/endpoints:

Extensive characterization will be done before, during, and after the intervention. Primary outcome measure is whole-body insulin sensitivity (Matsuda index) assessed by means of a 7-point oral glucose tolerance test (OGTT). Secondary outcomes include glycaemic variability, mean glucose levels, fasting lipid profiles, body composition, blood pressure, gene and protein expression of adipose tissue, microbial composition and functionality, metabolomics, physical activity, adherence to dietary recommendations, (mental) well-being, and quality of life.

Eligibility criteria: Inclusion Criteria:

* Men and women with a BMI ≥25 to \<40 kg/m2
* Classification possible to one of the investigational metabolic phenotypes according to the classification algorithm.
* Weight stability for at least 3 months (+/- 3 kg)

Exclusion Criteria:

Diseases

* (Pre-)diagnosis of type 1 or type 2 diabetes mellitus (i.e., FPG ≥ 7,0 mmol/L) and HbA1c ≥ 6,5% (48 mmol/mol)
* Renal or hepatic malfunctioning (pre-diagnosis or determined based on ALAT and creatinine values)
* Gastrointestinal diseases or abdominal surgery (allowed i.e.:

appendectomy, cholecystectomy)

* Food allergies, intolerances (including gluten/lactose intolerance) and/or eating disorders interfering with the study
* Cardiovascular diseases (e.g., heart failure) or cancer (e.g., noninvasive skin cancer allowed)
* High systolic blood pressure (untreated \>160/100 mmHg, drug-regulated \>140/90 mmHg)
* Diseases affecting glucose and/or lipid metabolism (e.g., pheochromocytoma, Cushing's syndrome, acromegaly)
* Diseases with a life expectation shorter than 5 years
* Major mental disorders
* Drug treated thyroid diseases (well substituted hypothyroidism is allowed inclusion)
* Other physical/mental conditions that may interfere with study outcomes

Medication

* Medication known to interfere with study outcomes (e.g., PPAR-α or PPAR-γ agonists (fibrates), sulfonylureas, biguanides, α-glucosidaseinhibitors, thiazolidinediones, repaglinide, nateglinide, insulin, and chronic use of NSAIDs)
* Use of certain anticoagulants other than acetylsalicylic acid
* Use of antidepressants (stable use ≥ 3 months prior to and during study allowed)
* Use of statins (stable use ≥ 3 months prior to and during study allowed)
* Chronic corticosteroids treatment (\>7 consecutive days of treatment)
* Use of antibiotics within 3 months prior to the study

Lifestyle

* Participation in regular sports activities (moderate-to-vigorous physical exercise \>4 hours per week)
* Having a restricted dietary pattern interfering with the study diets (e.g., vegetarian, vegan, Atkins diet and/or other special diets)
* Plans to lose or gain more than 5% body weight
* Abuse of alcohol (alcohol consumption \>14 units/week) and/or drugs (cannabis included)
* Not willing to limit alcohol consumption to 7 drinks per week
* Regular smoking (including use of e-cigarettes and vapes)
* Use of strong vitamins or other dietary supplements (e.g., pre- or probiotics) expected to interfere with the study outcomes

Other

* Metabotype classification is not possible
* Pregnant or lactating women, or women who are planning to become pregnant
* Inability to comply with the study diet
* Blood donation within the last 3 months
* Participation in possibly interfering studies within the last 3 months
* Inability to understand study information and/or communicate with staff
* Unwillingness to be randomised or sign informed consent
* Unwillingness to save data for 15 years
* Deemed unsuitable for participation in the trial, for any reason, as judged by the research physician or principal investigator

Primary outcomes:
measure: Matsuda Index
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
Secondary outcomes:
measure: Glucose tolerance
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Disposition Index (DI)
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: HOMA-IR
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Muscle insulin sensitivity (MISI)
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Hepatic insulin resistance (HIRI)
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Adipose tissue insulin sensitivity (ATIRI)
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Insulinogenic Index (IGI)
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: HOMA-β
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Circulating hormones such as Insulin
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Body composition
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Waist circumference
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Hip circumference
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Waist-to-hip ratio (WHR)
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Subcutaneous adipose tissue gene expression
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Subcutaneous adipose tissue protein expression
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Blood pressure
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Mean 24h glucose concentrations
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Glucose incremental area under the curve (iAUC)
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: The frequency of hypo- and hyperglycemia
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Mean Amplitude of Glucose Excursions (MAGE)
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Time in Range (TIR)
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Coefficient of Variation (CV%)
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Standard Deviation (SD) of Glucose Levels
timeFrame: Time Frame: Change from baseline at month 12 following dietary intervention.
measure: The duration of hypo- and hyperglycemia
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Gut microbial composition
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Circulating SCFA
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Targeted plasma metabolomics
timeFrame: Baseline
measure: Circulating lipids such as FFA
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Circulating inflammatory markers such as CRP
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Circulating HbA1c
timeFrame: Change from baseline at month 6 and month 12 following dietary intervention.
measure: Physical activity
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Self-reported self-efficacy
timeFrame: Change from baseline at month 6 and 12 following dietary intervention.
measure: Self-reported context-sensitive positive health
timeFrame: Change from baseline at month 1 and 12 following dietary intervention.
measure: Self-reported mood
timeFrame: Change from baseline at month 6 and 12 following dietary intervention.
measure: Self-reported stool consistency
timeFrame: Change from baseline at month 1 and 12 following dietary intervention.
measure: Self-reported fatigue
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Self-reported health-related quality of life
timeFrame: Change from baseline at month 1 and 12 following dietary intervention.
measure: Self-reported positive health
timeFrame: Change from baseline at month 1 and 12 following dietary intervention.
measure: Adherence to dietary recommendations
timeFrame: 12-months, continuously throughout the study
measure: Self-reported mental health
timeFrame: Change from baseline at month 6 and 12 following dietary intervention.
measure: Self-reported perceived stress
timeFrame: Change from baseline at month 6 and 12 following dietary intervention.
measure: Self-reported gastrointestinal health
timeFrame: Change from baseline at month 1 and 12 following dietary intervention.
measure: Self-reported sleep quality
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Self-reported daytime sleepiness
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: Self-reported chronotype
timeFrame: Change from baseline at month 12 following dietary intervention.
measure: DNA analysis
timeFrame: Baseline
Other outcomes:
measure: Baseline characteristics
timeFrame: Baseline
measure: Metabotype cluster
timeFrame: Baseline, and change from baseline at month 6 and month 12 following dietary intervention.
measure: Capillary Blood Samples (CBS)
timeFrame: Baseline and following 12 month dietary intervention.
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center, Department of Human Biology, NUTRIM Institute of Nutrition and Translational Research in Metabolism
city: Wageningen
country: Netherlands
facility: Wageningen University and Research, Division of Human Nutrition
Study officials:
affiliation: Maastricht University Medical Center
name: Ellen E Blaak, Prof. Dr. Ir.
role: PRINCIPAL_INVESTIGATOR
References: