Dapagliflozin As Additional Treatment To Liraglutide And Insulin In Patients With Type 1 Diabetes. A Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Absolute Change After 12 Weeks From Baseline in Mean HbA1c With Addition of Dapagliflozin Compared to Placebo.
研究概览
简要总结
This is a single center, prospective, randomized, double blinded placebo controlled study conducted I patients with type 1 diabetes.The aim of this study is to examine the additive effects of GLP-1 agonist and SGLT2 inhibitor in patients with type 1 diabetes in terms of possible improved glycemic control, reduced glycemic variability, reduced insulin dosages, additional effects of weight loss and blood pressure reduction.
详细描述
This investigation will be single center, prospective, randomized, double blinded placebo controlled study conducted in type 1 diabetics. The study will be conducted at Diabetes - Endocrinology Center of WNY, affiliated to the State University of New York at Buffalo.
Visit 1: Screening Day (day -21):- Each patient will have completed the following procedures prior to participating in the study.
- Medical History;
- Physical Exam;
- Informed consent.
- Baseline lab draws to measure CBC, comprehensive metabolic panel, Hba1c, Fructosamine and lipid profile. All labs will be drawn in the fasting state in the morning before 10am.
Visit 2: Randomization Visit (day -14): After the screening visit, subjects who meet the inclusion and exclusion criteria will participate in the study period. Randomization will be done by a ratio of 2:1(drug: placebo) using Microsoft Excel randomization function. Liraglutide will be obtained from Novo Nordisk pharmaceuticals. Dapagliflozin/placebo will be obtained from Astra Zeneca pharmaceuticals. All subjects will be instructed by the study staff in the dosing and administration of the study medication. Subjects will be seen by a registered dietitian who will review their carbohydrate counting and make an assessment of their carbohydrate intake. A CGM sensor will be inserted and the patient will be asked to keep it for 2 weeks. Detailed instruction on changing the sensor weekly will be provided and insulin titration will be done to control blood sugar between 70-180 mg/dl. A urine container to collect urine for 24 hours to measure 24-hour urinary glucose will be provided (urine to be collected one day before the next visit).
All subjects will be advised to monitor their capillary blood glucose by finger stick before each meal and at bedtime and to wear their CGM constantly for the first two weeks and the last two weeks of the study The subjects will be asked to keep a diary of their food intake to measure their carbohydrate intake. For the entire duration of the study, the patients will maintain a diary to record any hypoglycemia and other untoward side effects like nausea, changes in appetite and other experiences. Patients will be instructed to call the Diabetes Center or an endocrinology fellow directly in case of any problem or untoward side effects. They will be specifically asked to call if they have hypoglycemia (blood sugar <70 mg/dl) or hyperglycemia (blood sugar >250 mg/dl) on more than one occasion.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
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 and treatment with liraglutide at maximal tolerated doses for at least 6 months prior to start of the study.
- •Willing to use a continuous glucose monitoring device (CGM) and regularly measuring their blood sugars four times daily
- •HbA1c of less than or equal to 11%.
- •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
- •ESRD on hemodialysis; and or e-GFR less than 30 ml/min/1.73m2
- •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
- •Pregnancy
- •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
- •Women who are pregnant
- •History of serious hypersensitivity reaction to these agents.
研究组 & 干预措施
Placebo
12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo"
干预措施: Insulin (Drug)
Placebo
12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo"
干预措施: Liraglutide (Drug)
Placebo
12 weeks of treatment with Insulin, Liraglutide and "Dapagliflozin Placebo"
干预措施: Dapagliflozin placebo (Drug)
Active drugs
12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug"
干预措施: Dapagliflozin (Drug)
Active drugs
12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug"
干预措施: Insulin (Drug)
Active drugs
12 weeks of treatment with Insulin, Liraglutide and "Active Dapagliflozin Drug"
干预措施: Liraglutide (Drug)
结局指标
主要结局
Absolute Change After 12 Weeks From Baseline in Mean HbA1c With Addition of Dapagliflozin Compared to Placebo.
时间窗: 12 weeks
T1D. Conservatively estimating a difference in mean HbA1c (the primary end point) of 0.5% before and after the treatment, and a sample size of 30 (2:1 drug to placebo ratio) should provide adequate power (.8) to detect a significant difference (.05) provided the standard deviation of the residuals in not greater than 0.4%. The sample size includes an additional 20% to account for the potential dropout. Changes in these end points were calculated by averaging the differences in weekly average values from baseline.
次要结局
- Change in Time Spent at Normal Glucose Concentrations Between 70-160mg/dl(12 weeks)
- Change in 24-hour Urine Glucose Excretion.(12 weeks.)
- Change in Body Weight(12 weeks)
- Change in Systolic Blood Pressure Before and After Treatment(12 weeks)
- Change in Blood Ketone Bodies(12 weeks)
- Change in Total Daily Insulin Requirements(12 weeks)
研究者
Paresh Dandona
MD
University at Buffalo