Clinical trial NCT06003153: GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
Official title: GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Genetic Predisposition
Metabolic Diseases
Type 2 Diabetes
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-08-21
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 type 2 diabetes 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 oral semaglutide. 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 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.

Detailed description: On day 1 (Visit 1), the research subject will present to the Translational and Clinical Research Center (TCRC) after an overnight fast. We will obtain informed consent, check vital signs, take anthropometric measurements, and draw fasting blood work through an intravenous catheter. The subject will then be provided a standard mixed meal to be consumed within 30 minutes. Additional blood will be drawn at the time of meal completion (0 minutes), as well as 5, 15, 30, 60, 90, and 120 minutes following the meal. During study days 3-15, the subject will take 7 mg of oral semaglutide once daily. On day 16 (Visit 2), the research subject will return to the TCRC. During this visit, the subject will take the final (14th) dose of semaglutide, receive fasting blood work, and receive another mixed meal with subsequent blood draws at several time points over 120 minutes.

Eligibility criteria: Inclusion Criteria:

1. Males or non-pregnant females
2. Ages 18-50 (inclusive)
3. Able/willing to give consent
4. 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:

1. Currently taking medications or intending to take medications for diabetes
2. Currently taking medications or intending to take medications that affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones
3. Personal history of intestinal malabsorption, bariatric surgery, celiac disease, gallbladder disease, or pancreatitis
4. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
5. Estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73 m2 per the Modification of Diet in Renal Disease equation
6. History of cirrhosis and/or aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal
7. Dietary restrictions preventing consumption of a MMTT
8. Women who are pregnant, nursing, or at risk of becoming pregnant
9. Participation in other interventional studies during the current study

Primary outcomes:
measure: Insulin response to oral semaglutide treatment
timeFrame: 15 days
Secondary outcomes:
measure: Fasting glucose response to oral semaglutide treatment
timeFrame: 15 days
measure: Cumulative glucose response to oral semaglutide treatment
timeFrame: 15 days
measure: Baseline incretin level
timeFrame: 120 minutes during Visit 1
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: MGH
name: Josephine Li, MD
role: PRINCIPAL_INVESTIGATOR
References: