Back to resultsGLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH (GLUCOSE-MGH)
Primary Purpose
Genetic Predisposition, Metabolic Diseases, Type 2 Diabetes
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Mixed Meal Tolerance Test (MMTT)
Rybelsus
Sponsored by
About this trial
This is an interventional treatment trial for Genetic Predisposition
Eligibility Criteria
Inclusion Criteria: Males or non-pregnant females Ages 18-50 (inclusive) Able/willing to give consent Span the metabolic range between normal glycemia and pre-diabetes (fasting glucose of 100-125 mg/dL based on chart review of existing laboratory data) Exclusion Criteria: Currently taking medications or intending to take medications for diabetes Currently taking medications or intending to take medications that affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones Personal history of intestinal malabsorption, bariatric surgery, celiac disease, gallbladder disease, or pancreatitis Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 per the Modification of Diet in Renal Disease equation History of cirrhosis and/or aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal Dietary restrictions preventing consumption of a MMTT Women who are pregnant, nursing, or at risk of becoming pregnant Participation in other interventional studies during the current study
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
GLUCOSE-MGH Study
Arm Description
Day 1: Mixed meal tolerance test Day 3-15: 7mg Rybelsus, once daily Day 16: 1 dose of 7mg Rybelsus, Mixed meal tolerance test in the presence of Rybelsus
Outcomes
Primary Outcome Measures
Insulin response to oral semaglutide treatment
Investigators will measure the change in insulin area under the curve (AUC) over 120 minutes of the MMTT, calculated using the trapezoidal method, between Visit 1 and Visit 2 as an index of response to oral semaglutide, and compare this outcome by genotype at selected loci.
Secondary Outcome Measures
Fasting glucose response to oral semaglutide treatment
Investigators will measure the change in fasting glucose over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
Cumulative glucose response to oral semaglutide treatment
Investigators will measure the change in glucose area under the curve (AUC) over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
Baseline incretin level
Investigators will measure levels of GLP-1 during the length of the baseline MMTT (120 minutes) that takes place on Visit 1, and compare changes in the baseline levels by genotype at selected loci.
Full Information
NCT ID
NCT06003153
First Posted
August 9, 2023
Last Updated
August 18, 2023
Sponsor
Massachusetts General Hospital
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT06003153
Brief Title
GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
Acronym
GLUCOSE-MGH
Official Title
GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
December 30, 2027 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of this research study is to evaluate the pathophysiologic mechanisms by which genetic variation impacts response to an FDA-approved medication commonly used to treat diabetes and obesity called oral semaglutide (Rybelsus) and to characterize the physiological response to a mixed meal tolerance test (MMTT) before and after a 14-day treatment with Rybelsus. The effect of oral semaglutide (Rybelsus) on human beings is similar regardless of whether the person taking them has diabetes or not. The investigators will do this by measuring factors in the blood, such as sugars, fats, metabolites, and proteins, after eating a standardized breakfast meal at the first visit and after taking 14 doses of oral semaglutide (Rybelsus) over two weeks before the second study visit. The food (mixed meal breakfast) we will be studying is specially prepared to contain a set amount of protein, carbohydrates, and fat. The investigators hypothesize that understanding how the acute biochemical response to oral semaglutide differs by genetic variation will generate insight into drug mechanisms and Type 2 Diabetes pathophysiology.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Genetic Predisposition, Metabolic Diseases, Type 2 Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
125 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GLUCOSE-MGH Study
Arm Type
Other
Arm Description
Day 1: Mixed meal tolerance test
Day 3-15: 7mg Rybelsus, once daily
Day 16: 1 dose of 7mg Rybelsus, Mixed meal tolerance test in the presence of Rybelsus
Intervention Type
Other
Intervention Name(s)
Mixed Meal Tolerance Test (MMTT)
Intervention Description
The MMTT meal will provide a standard amount of total calories, protein, fat and carbohydrate to each participant at both study visits. Pre-packaged and freshly prepared food will be given in this MMTT. The participants will undergo a MMTT at Visit 1 and Visit 2.
Intervention Type
Drug
Intervention Name(s)
Rybelsus
Other Intervention Name(s)
Oral Semaglutide
Intervention Description
Rybelsus will be administered during this study. This medication is safely prescribed for the treatment of type 2 diabetes and obesity. We will give 14 doses (7mg each dose) to study participants over 14 days. Another MMTT will be performed after the 14th dose of Rybelsus.
Primary Outcome Measure Information:
Title
Insulin response to oral semaglutide treatment
Description
Investigators will measure the change in insulin area under the curve (AUC) over 120 minutes of the MMTT, calculated using the trapezoidal method, between Visit 1 and Visit 2 as an index of response to oral semaglutide, and compare this outcome by genotype at selected loci.
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Fasting glucose response to oral semaglutide treatment
Description
Investigators will measure the change in fasting glucose over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
Time Frame
15 days
Title
Cumulative glucose response to oral semaglutide treatment
Description
Investigators will measure the change in glucose area under the curve (AUC) over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
Time Frame
15 days
Title
Baseline incretin level
Description
Investigators will measure levels of GLP-1 during the length of the baseline MMTT (120 minutes) that takes place on Visit 1, and compare changes in the baseline levels by genotype at selected loci.
Time Frame
120 minutes during Visit 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males or non-pregnant females
Ages 18-50 (inclusive)
Able/willing to give consent
Span the metabolic range between normal glycemia and pre-diabetes (fasting glucose of 100-125 mg/dL based on chart review of existing laboratory data)
Exclusion Criteria:
Currently taking medications or intending to take medications for diabetes
Currently taking medications or intending to take medications that affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones
Personal history of intestinal malabsorption, bariatric surgery, celiac disease, gallbladder disease, or pancreatitis
Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 per the Modification of Diet in Renal Disease equation
History of cirrhosis and/or aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal
Dietary restrictions preventing consumption of a MMTT
Women who are pregnant, nursing, or at risk of becoming pregnant
Participation in other interventional studies during the current study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Varinderpal Kaur
Phone
6176435419
Email
vkaur@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Josephine Li
Phone
617-643-4987
Email
jli71@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josephine Li, MD
Organizational Affiliation
MGH
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
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