Effect of Novel Glucagon Receptor Antagonist REMD-477 on Glucose and Adipocyte Metabolism in Type 2 Diabetes Mellitus (T2DM)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Glycated Hemoglobin (HbA1c)
研究概览
简要总结
With REMD's glucagon receptor antagonist, the study team propose to provide a comprehensive examination of the effect of elevated plasma glucagon concentrations in Type 2 Diabetes Mellitus (T2D) patients on:
(i) glucose tolerance; (ii) insulin sensitivity in liver, muscle, and adipocytes; (iii) beta cell function; (iv) adipocyte inflammation.
详细描述
Subjects with T2DM inadequately controlled on current medications will participate in a glucose tolerance test, euglycemic insulin clamp combined with 3-3H-glucose and 14-C glycerol infusion, adipose tissue biopsy, before and 12 weeks after treatment with REMD 477 or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Participants will be blinded to the study drug or placebo randomization.
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
- 否
入选标准
- •Type 2 diabetic subjects, males/females;
- •age = 18-70 years
- •BMI = 25-40 kg/m2;
- •HbA1c = 7.5-10.0%;
- •Type 2 Diabetics who are drug naïve or treated with metformin, sulfonylureas, SGLT-2 inhibitors or any combination thereof.
- •Subjects must be on a stable dose of antidiabetic medications for at least 3 months prior to study.
- •Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- •Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period
排除标准
- •Subjects with a personal or family history of pancreatic neuroendocrine tumors or multiple endocrine neoplasia, due to the potential increased of pancreatic alpha cell carcinogenicity associated with glucagon receptor antagonists.
- •Subjects with a contraindication to MRI including artificial heart valves or pacemakers
- •Patients with a known sensitivity to humanized antibodies
- •Subjects treated with GLP-1 RAs or insulin are excluded.
- •Subjects treated with a non-antidiabetic medication that may impact insulin sensitivity, such as systemic steroids, or lipase inhibitors (orlistat, Alli or Xenical)
- •Hematocrit < 34 vol%
- •Serum creatinine > 1.8 mg/dl
- •AST (SGOT) > 2 times upper limit of normal
- •ALT (SGPT) > 2 times upper limit of normal
- •Any major organ system disease as identified by medical history, physical exam, and screening blood tests, EKG
- •Subjects who cannot give written, voluntary consent
- •Subjects with a major psychiatric disturbance
- •Only subjects whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.
- •Patients must not have type 1 diabetes
- •Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c > 10.0%
- •Patients must not have received a thiazolidinedione, GLP-1 agonist, or insulin for more than one week during the year prior to randomization
- •Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
研究组 & 干预措施
Glucagon Receptor Agonist (GRA) REMD-477 group
Participants are assigned to a 12 week treatment of REMD-477
干预措施: REMD-477 (Drug)
Placebo group
Participants are assigned to a 12 week course of placebo for REMD-477
干预措施: Placebo Subcutaneous injection (Drug)
结局指标
主要结局
Glycated Hemoglobin (HbA1c)
时间窗: Baseline to 13 weeks
Change in HbA1c measured at baseline and after intervention administration
Fasting Plasma glucose (FPG)
时间窗: Baseline to 13 weeks
Change in fasting plasma glucose measured at baseline and after intervention administration
Plasma glucose (PG)
时间窗: Baseline to 13 weeks
Change in plasma PG measured at baseline and after intervention administration using an oral glucose tolerance test (OGTT)
Hepatic insulin sensitivity
时间窗: Baseline to 13 weeks
Change in hepatic glucose production (HGP)
Whole body glucose disposal
时间窗: Baseline to 13 weeks
Change in whole body glucose disposal measured in mg/kg/min
Plasma Free Fatty Acids (FFA)
时间窗: Baseline to 13 weeks
Change in plasma free fatty acids
Muscle Insulin sensitivity
时间窗: Baseline to 13 weeks
Change in muscle insulin sensitivity measured by insulin-stimulated glucose uptake during low dose high dose insulin clamp.
次要结局
未报告次要终点