PREMIER: PREvention of Metabolic Illness Through prEcision nutRition

NCT04148482 | Completed Results DMC

• 2 other identifiers: 2019P002638P30DK040561
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Type 2 Diabetes; Metabolic Syndrome; Diet Habit; Nutritional and Metabolic Disease; Food Preferences

Outcome Measures

Primary Outcomes (2)

• Glucose at Times 30min, 60min, 120min, 180min

  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

Secondary Outcomes (1)

• Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline)

  Day 1

Other Outcomes (1)

• Previously Proposed Outcomes: Hunger Perception, Incretin Levels by Immunoassay Kit, Satiety Hormones

  baseline, 120min, 240min, 360min

Study Arms (2)

Genotype of interest group

ACTIVE COMPARATOR

Individuals with desired genetic susceptibility will receive a standardized and an election meal in a full-day clinic visit.

Other: Dietary intervention

Control

PLACEBO COMPARATOR

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

Interventions

Dietary intervention OTHER

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.

Control; Genotype of interest group

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female.
• years of age.
• Body mass index (BMI) between 18.5 and 30.0 kg/m2.

You may not qualify if:

• Willing to comply with the study intervention.
• Able to provide informed consent
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Massacusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2; Metabolic Syndrome; Feeding Behavior; Metabolic Diseases; Food Preferences

Interventions

Diet Therapy

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Endocrine System Diseases; Insulin Resistance; Hyperinsulinism; Behavior, Animal; Behavior

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics

Results Point of Contact

• Title: Sara Cromer
• Organization: Massachusetts General Hospital

scromer@mgh.harvard.edu

6177247303

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a recall-by-genotype study

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: November 1, 2019
• Study Start: June 17, 2021
• Primary Completion: September 19, 2024
• Study Completion: September 19, 2024
• Last Updated: July 23, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 6-12 months after finishing the study intervention

Locations

US (1)