Study of Clinical Response to Acute Metformin By Leveraging Evaluations During a Mixed Meal Tolerance Test for Exploring Glycemia and GeneticS (SCRAMBLED EGGS)

Study of Clinical Response to Acute Metformin By Leveraging Evaluations During a Mixed Meal Tolerance Test for Exploring Glycemia and GeneticS (SCRAMBLED EGGS)

The purpose of this research study is to examine whether specific genes (e.g. SLC16A11) affect how human beings respond to food and a medication that is commonly used to treat type 2 diabetes. The food the investigators will be studying is specially prepared to contain protein, carbohydrate, and fat. The drug the investigators are studying is metformin. The investigators hypothesize that physiological responses to the meal and to the medication will differ between carriers and non-carriers of genes associated with type 2 diabetes.

Study Overview

• Status: Active, not recruiting
• Conditions: Type 2 Diabetes; Genetics; Metabolism
• Intervention / Treatment: Other: Mixed Meal Tolerance Test; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 1017
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult males or non-pregnant females
• Age 18-79
• Able and willing to give consent relevant to genetic investigation

Exclusion Criteria:

• Women who are pregnant, nursing, or at risk of becoming pregnant
• Currently taking any medications used for the treatment of diabetes
• History of liver disease and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation
• Currently taking or intending to take during the study duration any medication known to affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones
• Contraindications to safe use of metformin, including planned radiologic or angiographic study requiring contrast within one week of the study completion
• Planned changes to any prescribed medications, specifically diuretics, during study enrollment
• Participation in any other interventional study during the study duration
• Conditions causing intestinal malabsorption, including celiac disease or a history of intestinal or gastric bypass surgery
• Dietary restrictions that would prevent consumption of a MMTT
• Objection or inability to take metformin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Carriers of the SLC16A11 risk allele; Day 1: Mixed Meal Tolerance Test Day 3-7: 500mg metformin, twice daily Day 8: Mixed Meal Tolerance Test in presence of Metformin	Other: Mixed Meal Tolerance Test; The meal will provide a standard amount of total calories, protein, fat, and carbohydrate to each participant at both study visits. Pre-packaged and prepared food, weighed to the nearest gram, will be used.; Drug: Metformin; Metformin will be administered during this study. This medication is safely prescribed at a maximum dose of 1000 mg twice daily for the treatment or prevention of type 2 diabetes, as well as for other metabolic conditions. To minimize potential side effects of metformin (e.g., GI upset), participants will take ½ the maximum dose of this medication (500 mg twice daily) and for only 5 days. Participants will be informed of the potential side effects of metformin. They will be asked to contact study staff and discontinue the medication if symptoms are very uncomfortable.; Other Names: Glucophage; Glucophage XR; Glumetza; Fortamet
Placebo Comparator: Non-carriers of the SLC16A11 risk allele; Day 1: Mixed Meal Tolerance Test Day 3-7: 500mg metformin, twice daily Day 8: Mixed Meal Tolerance Test in presence of Metformin	Other: Mixed Meal Tolerance Test; The meal will provide a standard amount of total calories, protein, fat, and carbohydrate to each participant at both study visits. Pre-packaged and prepared food, weighed to the nearest gram, will be used.; Drug: Metformin; Metformin will be administered during this study. This medication is safely prescribed at a maximum dose of 1000 mg twice daily for the treatment or prevention of type 2 diabetes, as well as for other metabolic conditions. To minimize potential side effects of metformin (e.g., GI upset), participants will take ½ the maximum dose of this medication (500 mg twice daily) and for only 5 days. Participants will be informed of the potential side effects of metformin. They will be asked to contact study staff and discontinue the medication if symptoms are very uncomfortable.; Other Names: Glucophage; Glucophage XR; Glumetza; Fortamet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to the Mixed Meal Tolerance Test	Primary endpoint point: 2 hr glucose after the MMTT Secondary endpoints: 2 hr insulin after the MMTT, change in glucose, insulin, and amino acid and lipid metabolites from baseline to 60 and 120 minutes after the MMTT; change in GLP-1 concentrations from baseline to 5,10, 15, 30, 60, and 120 minutes after the MMTT; and glucose, insulin, and GLP-1 AUC over 120 minutes	2 hours after the meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to Metformin	Primary endpoint: change in fasting glucose from Visit 1 to Visit 2 Secondary endpoints: change in fasting insulin, amino acid and lipid metabolites, GLP-1, and HOMA-IR from Visit 1 to Visit 2	Day 8 of the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to a Mixed Meal Tolerance Test after Metformin	Primary endpoint point: 2 hr glucose after the MMTT Secondary endpoints: 2 hr insulin after the MMTT, change in glucose, insulin, and amino acid and lipid metabolites from baseline to 60 and 120 minutes after the MMTT; glucose, insulin, and GLP-1 AUC over 120 minutes; and intra-individual change in the above variables from Visit 1 to Visit 2	2 hours after the meal

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Broad Institute; Instituto Carlos Slim de la Salud
• Investigators: Study Director: Jose C Florez, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 2014P000255