Ghrelin Effect on Beta Cell Function in Health and Disease #2
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Index of β-cell sensitivity to glucose
研究概览
简要总结
Ghrelin is a hormone naturally produced in the stomach and the gut. The purpose of this research study is to determine the role of this gut hormone in the regulation of insulin secretion from the pancreas and glucose disposal after we eat. The investigators hypothesize that ghrelin has an effect on the pancreas and on how our body handles glucose after we eat. The investigators will compare insulin secretion and glucose changes during meal ingestion while either acyl ghrelin (AG) or saline (salt solution) is being infused through your vein on separate study days. AG is a form of the ghrelin hormone that has a small modification to it that allows it to bind to a specific receptor. The investigators hypothesize that AG has an effect on how the body handles glucose after a meal. AG has been approved by the U.S. Food and Drug Administration (FDA) for human research only. This study will also involve the use of a medicine called arginine, which is a naturally occurring product and found in many nutritional supplements. Its use in this study is investigational. The use of arginine helps maximize insulin release from the pancreas so the investigators can better examine whether AG affects insulin secretion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •T2DM study subjects to be considered for the study must meet the following inclusion criteria:
- •Established T2DM with good to moderate glycemic control
- •HbA1c < 8.5%
- •Diabetes treatment with metformin, sulfonylurea, thiazolidinediones or combination of these medications; with no use of insulin during the study period
- •BMI ≤ 45.0 kg/m2
- •Control study subjects will be matched for age- (± 2 years), BMI (± 1.5 kg/m2) and gender and must meet the following inclusion criteria:
- •HbA1c ≤ 5.7%
- •Fasting plasma glucose ≤ 95 mg/dL
- •BMI ≤ 45.0 kg/m2
排除标准
- •All subjects will be excluded for the following reasons:
- •History of myocardial infarction or arrhythmia within the past year, abnormal electrocardiogram (ECG) with evidence of ischemia or arrhythmia, history or symptoms of congestive heart failure
- •Uncontrolled hypertension
- •History or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [eGFR] <60 at screening)
- •History of pituitary or adrenal disorders or neuroendocrine tumor
- •Anemia defined as hematocrit <33% at screening
- •Active cancer diagnosis or currently undergoing cancer treatment
- •History of anorexia nervosa or previous gastrointestinal tract surgery
- •Pregnancy or lactation
- •Control subjects will be excluded for the following reasons:
- •History or clinical evidence of impaired fasting glucose or impaired glucose tolerance on a 75 g OGTT, established diabetes mellitus, or taking medications prescribed for diabetes
- •Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin)
研究组 & 干预措施
Study Group: Type 2 Diabetes Mellitus (T2DM)
Subjects with Type 2 Diabetes Mellitus (T2DM). Subjects will receive AG and saline infusions, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
干预措施: Synthetic human AG (Drug)
Study Group: Type 2 Diabetes Mellitus (T2DM)
Subjects with Type 2 Diabetes Mellitus (T2DM). Subjects will receive AG and saline infusions, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
干预措施: Arginine (Drug)
Study Group: Type 2 Diabetes Mellitus (T2DM)
Subjects with Type 2 Diabetes Mellitus (T2DM). Subjects will receive AG and saline infusions, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
干预措施: 0.9% saline solution (Drug)
Control Group
Control group of healthy subjects. Subjects will receive AG and saline, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
干预措施: Synthetic human AG (Drug)
Control Group
Control group of healthy subjects. Subjects will receive AG and saline, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
干预措施: Arginine (Drug)
Control Group
Control group of healthy subjects. Subjects will receive AG and saline, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
干预措施: 0.9% saline solution (Drug)
结局指标
主要结局
Index of β-cell sensitivity to glucose
时间窗: approximately 8 weeks
Index of β-cell sensitivity to glucose will be calculated as incremental insulin/glucose (I/G) AUC (ΔAUCI/G).
Whole body insulin sensitivity using the Matsuda Index
时间窗: approximately 8 weeks
The Matsuda Index is a well-known index of insulin sensitivity derived from several glucose and insulin values obtained during a mixed meal
Postprandial insulin secretion (ISR-meal)
时间窗: approximately 8 weeks
Postprandial insulin secretion (ISR-meal) will be derived from plasma C-peptide concentrations during MTT (0-240 min) using deconvolution with population estimates of C-peptide clearance.
β-cell function (DI-meal)
时间窗: approximately 8 weeks
β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index
次要结局
未报告次要终点
研究者
Jenny Tong, MD, MPH
Associate Professor
Duke University