PREMIER: PREvention of Metabolic Illness Through prEcision nutRition (PREMIER)

Dietary intake is a major driving force behind the escalating obesity and type 2 diabetes epidemics. Large, high-quality clinical trials have shown that close adherence to healthy dietary recommendations significantly reduce the incidence of obesity and type 2 diabetes, especially among people at increased risk. However, large inter-individual variability exists in response to dietary interventions. To inform more effective obesity and type 2 diabetes prevention strategies, it is crucial to better understand the biological, environmental, and social factors that influence how people interact and respond to specific foods.

In a recent large-scale genome-wide association study, our research team has identified 96 genomic regions associated with overall variation in dietary intake. This study provided evidence that inherited molecular differences are likely to impact on food intake (i.e., preference for certain foods) and metabolic homeostasis (i.e., glucose regulation). Connecting knowledge about human genetic variants with information from circulating metabolites can be particularly useful in understanding the mechanisms by which some people experience a detrimental response to specific foods.

The specific objective of the PREMIER study is to carry out an interventional dietary study to measure the response of blood glucose and other biomarkers to a standardized meal, and evaluate the extent to which food choices differ among individuals with distinct genetic susceptibility.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity; Metabolic Syndrome; Type 2 Diabetes; Food Preferences; Diet Habit; Nutritional and Metabolic Disease
• Intervention / Treatment: Other: Dietary intervention

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massacusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female.
• 21-65 years of age.
• Body mass index (BMI) between 18.5 and 30.0 kg/m2.
• Healthy (free of diagnosed diseases listed in the exclusion criteria).
• Willing to comply with the study intervention.
• Able to provide informed consent

Exclusion Criteria:

• Refuse or are unable to give informed consent to participate in the study.
• Have type I or type II diabetes mellitus or are taking medications for type II diabetes mellitus. Those not on medications but having a capillary glucose level of >126 mg/dL based on fingertip glucose measurements will be excluded.
• Are obese (BMI>30.0kg/m2) or underweight (BMI<18.5kg/m2).
• Have had a heart attack (myocardial infarction) or stroke
• Have had cancer in the last 3 years, excluding skin cancer.
• Have an ongoing inflammatory disease i.e. Rheumatoid arthritis, systemic lupus erythematosus, polymyalgia and other connective tissue diseases.
• History of cirrhosis and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times the upper limit of normal (ULN).
• Are currently suffering from acute clinically diagnosed depression.
• Currently taking or intending to take during the study duration any medication known to affect glycemic parameters, such as glucocorticoids or fluoroquinolones.
• Are unable to fast from 9pm the night before the clinic visit until 9am on the clinic day
• Are pregnant or breastfeeding.
• Are participating in another clinical study.
• Are vegan, suffering from an eating disorder or unwilling to eat foods that are part of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Genotype of interest group; Individuals with desired genetic susceptibility will receive a standardized and an election meal in a full-day clinic visit.	Other: Dietary intervention; To investigate whether individuals with divergent genetic susceptibility have different food preferences and have differential post-prandial glycemic and metabolomics responses to a standardized or an election meal.
Placebo Comparator: Control; Individuals without genotype of interest (i.e., carrying the opposite genotype) will receive a standardized and an election meal in a full-day clinic visit.	Other: Dietary intervention; To investigate whether individuals with divergent genetic susceptibility have different food preferences and have differential post-prandial glycemic and metabolomics responses to a standardized or an election meal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose	Measurement of blood glucose at regular intervals.	Day 1
High-fat meal preference	Number of participants with preference for a high-fat meal.	Day 1
Hunger perception before and after test meals consumption using visual analogue scales	Record of hunger perception before and after test meals using visual analogue scales. Participants will provide ratings raging from 0 to 100 based on six questions commonly used in visual analogue scales including: "How hungry do you feel?" (0=not at all hungry / 100=as hungry as I've ever felt); "How full do you feel?" (100=not at all full / 0=as full as I have ever felt); "How strong is your desire to eat?" (0=very weak / 100=very strong); "How much do you think you could eat now?" (0=nothing at all / 100=a large amount); "Urge to eat" (0=no urge to eat / 100=strong, want to eat now, waiting is very uncomfortable); "Preoccupation with thoughts of food" (0=no thoughts of food / 100=very preoccupied difficult to concentrate on other things). The minimum and maximum values range from 0 to 100, with higher numbers indicating higher hunger perception.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics by mass spectrometry analysis	Investigators will perform metabolomic profiling of plasma samples at regular intervals by using both targeted and untargeted approaches on an existing platform that measures ~10000 metabolites (both polar and non-polar); they will compare their relative concentrations by genotype at selected loci before and after the interventions.	Day 1
Incretin levels by immunoassay kits	Measurement of blood Glucagon-Like Peptide-1 (GLP-1) and Gastric Inhibitory Polypeptide (GIP) concentrations at regular intervals	Day 1
Appetite satiety hormones levels by immunoassay kits	Measurement of blood Ghrelin, Leptin, Peptide YY (PYY), and Cholecystokinin (CCK) at regular intervals.	Day 1

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NORCH (Nutrition Obesity Research Center at Harvard); Boston Area Diabetes Endocrinology Research Center

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2021
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 28, 2024

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Metabolic Diseases
• Other Study ID Numbers: 2019P002638; P30DK040561 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Our research team will provide a personalized report containing individual's glycemic responses and potentially other biomarker responses to meals consumed by the end of the study.
• IPD Sharing Time Frame: 6-12 months after finishing the study intervention
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No