Liraglutide in the Treatment of Type 1 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Change in Mean Weekly Glucose Concentrations
研究概览
简要总结
Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases fasting, postprandial and the overall mean glucose concentrations.
Aim 1.1: To compare the mean fasting, the mean weekly glucose and the standard deviation of weekly blood glucose concentrations as recorded by continuous glucose monitoring prior to and following 6 weeks and 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. In addition, the time spent at glucose concentrations >150 and 200mg/dl and <70 and <40 mg/dl will also be compared.
Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. Glucose concentrations will be measured as areas under the curve for the data obtained from the meal challenge.
Aim 1.3: To compare HbA1c levels(glycated hemoglobin) before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases postprandial glucagon concentrations and increases postprandial C-peptide concentrations.
Aim 2.1: To compare fasting and postprandial glucagon and C-peptide concentrations following a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily.
Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric emptying.
Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily.
详细描述
RESEARCH DESIGN AND METHODS This investigation will be a prospective, randomized, double blind, placebo controlled study conducted in type 1 diabetics. The study will be conducted at Diabetes - Endocrinology Center of WNY at Millard Fillmore Hospital, affiliated to the State University of New York at Buffalo.
Study Population: Seventy two patients with type 1 diabetes on treatment with either continuous subcutaneous insulin infusion (CSII; also known as insulin pump) or multiple (four or more) injections of insulin per day will be included in the study. They will be randomized into 4 groups of 18 patients each. The patients will be randomized to placebo or 0.6 mg, 1.2 mg or 1.8 mg liraglutide daily. In view of the possibility of hypoglycemia and the side effect of nausea all patients will be started on 0.6 mg of liraglutide per day. The dose will then be titrated up to 1.2 and 1.8 mg on a weekly basis. No increases will be made once the target dose has been achieved in each group. Subjects will be recruited from our own patients, our existing database and from advertisements. The following insulin preparations will be used in the study: insulin detemir, glargine, aspart, glulisine and lispro. Subjects will continue to obtain their insulin supplies from their respective pharmacies.
STUDY DESIGN:
Screening Day (day -14):- Each patient will have completed the following procedures prior to participating in the study.
- Medical History;
- Physical Exam;
- Informed consent.
- Baseline lab draw to measure Complete blood count, comprehensive metabolic panel, Hba1c and lipid profile. All labs will be drawn in the fasting state in the morning before 10am.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Patients with type 1 diabetes mellitus: Fasting c-peptide < 0.1nmol/l on insulin therapy for more than 12 months with or without history of diabetic ketoacidosis.
- •Using a continuous glucose monitoring device (CGM) and regularly measuring their blood sugars four times daily
- •HbA1c of less than 8.5%.
- •Well versed with carbohydrate counting
- •Age 18-75 years
排除标准
- •Type 1 diabetes for less than 12 months;
- •Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks;
- •Hepatic disease (transaminase > 3 times normal) or cirrhosis;
- •Renal impairment (serum creatinine > 1.5);
- •HIV or Hepatitis C positive status;
- •Participation in any other concurrent clinical trial;
- •Any other life-threatening, non-cardiac disease;
- •Use of an investigational agent or therapeutic regimen within 30 days of study.
- •history of pancreatitis
- •inability to give informed consent
- •history of gastroparesis
- •history of medullary thyroid carcinoma or MEN 2 syndrome.
- •Family history of MEN 2, Family history of medullary thyroid cancer, or familial medullary thyroid cancer
- •Women of childbearing potential who are not using adequate contraception 16) Women who are pregnant
研究组 & 干预措施
Placebo
Daily Injection
干预措施: Placebo (Drug)
Liraglutide 1.8mg
Daily Injection
干预措施: Liraglutide (Drug)
Liraglutide 1.2mg
Daily injections
干预措施: Liraglutide (Drug)
Liraglutide 0.6 mg
Daily injection
干预措施: Liraglutide (Drug)
结局指标
主要结局
Change in Mean Weekly Glucose Concentrations
时间窗: 12 Weeks
The primary endpoint of the study is to detect a difference from baseline in mean weekly blood glucose concentrations before and after 12 weeks of treatment in each of the Liraglutide groups.
次要结局
- Change in HbA1c(12 Weeks)
- Change in Body Weight From Baseline(12 weeks)
- Change in Total Insulin Dose From Baseline(12 weeks)
- Change in the Area Under Curve (AUC) of Glucose Following the Meal(12 weeks)
- Change in Carbohydrate Intake(12 weeks)
- Change in Glucagon Concentrations(12 weeks)
研究者
Paresh Dandona
Distinguished Professor of Medicine
University at Buffalo