GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 125
- 试验地点
- 1
- 主要终点
- Insulin response to oral semaglutide treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or non-pregnant females
- •Ages 18-65 (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)
排除标准
- •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
研究组 & 干预措施
GLUCOSE-MGH Study
Day 1: Mixed meal tolerance test
Day 3-15: 7 mg oral semaglutide, once daily
Day 16: 1 dose of 7 mg oral semaglutide, Mixed meal tolerance test in the presence of semaglutide
干预措施: Mixed Meal Tolerance Test (MMTT) (Other)
GLUCOSE-MGH Study
Day 1: Mixed meal tolerance test
Day 3-15: 7 mg oral semaglutide, once daily
Day 16: 1 dose of 7 mg oral semaglutide, Mixed meal tolerance test in the presence of semaglutide
干预措施: oral semaglutide (Drug)
结局指标
主要结局
Insulin response to oral semaglutide treatment
时间窗: 15 days
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.
次要结局
- Fasting glucose response to oral semaglutide treatment(15 days)
- Cumulative glucose response to oral semaglutide treatment(15 days)
- Baseline incretin level(120 minutes during Visit 1)
研究者
Josephine Li, MD
Assistant Professor of Medicine
Massachusetts General Hospital