Adding Liraglutide to High Dose Insulin: Breaking the Cycle
2017年12月15日 更新者：Ildiko Lingvay
The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (>1.8 units/kg/day) in patients with uncontrolled (HbA1c >7.5%) type 2 diabetes mellitus will improve blood sugar control.
It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.
研究概览
详细说明
Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.
Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.
The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.
研究类型
介入性
注册 (实际的)
71
阶段
- 第四阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Texas
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Dallas、Texas、美国、75390
- Ut Southwestern
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Type 2 diabetes mellitus
- Insulin dose of >1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)
- HbA1c ≥ 7.5% and ≤ 11%
- Age ≥ 18
- Stable comorbidities on stable treatment regimens
- Stable dose of all oral hypoglycemics for ≥ 3 months prior to enrollment
- Ability to provide informed consent before any trial-related activities
Exclusion Criteria:
- Type 1 diabetes mellitus
- Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)
- History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)
- End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c
- Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)
- Unstable or decompensated comorbidities
- Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome
- Severe gastroparesis
- Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures
- Organ transplant recipient or waiting list candidate
- Steroid use (current or potential use during the trial)
- Known/suspected allergy to trial medication, excipients, or related products
- Contraindications to study medications, worded specifically as stated in the product's prescribing information
- Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器：利拉鲁肽
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Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
其他名称：
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安慰剂比较：生理盐水注射
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Placebo injection of 1.8mg saline once daily for 6-months
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Glycemic Control Measured by HbA1c
大体时间：6-months
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HbA1c (%)
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6-months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Pancreatic and Hepatic Triglyceride Content
大体时间：6-months
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Liver Triglyceride and Pancreatic Triglyceride
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6-months
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Weight
大体时间：6-months
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6-months
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Beta-Cell Function
大体时间：6-months
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Fasting Glucose as a Measure of Beta-Cell Function
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6-months
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Glucagon
大体时间：6-months
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Measured during mixed meal challenge test.
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6-months
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Total Daily Insulin Dose
大体时间：6-months
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The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.
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6-months
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Number of Daily Injections
大体时间：6-months
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The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.
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6-months
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Blood Pressure
大体时间：6-months
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6-months
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|
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Lipid Profile
大体时间：6-months
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6-months
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Liver Function Blood Test
大体时间：6-months
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6-months
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Hypoglycemic Events
大体时间：6-months
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Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl
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6-months
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Quality of Life Survey (QoL) - General Health Perception
大体时间：6-months
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General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor.
|
6-months
|
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Beta-Cell Function
大体时间：6 months
|
Fasting C-peptide as a Measure of Beta-Cell Function
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6 months
|
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Matsuda Index as a Measure of Beta Cell Function
大体时间：6 months
|
The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values.
Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)).
Higher/lower values = better/worse insulin sensitivity.
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6 months
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Beta-cell Function
大体时间：6 Months
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AUC c-peptide
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6 Months
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Ratio (AUC C-peptide/AUC Glucose)
大体时间：6 months
|
6 months
|
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AUC Glucose
大体时间：6 months
|
6 months
|
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Quality of Life Survey (QoL) - Current Health Perception
大体时间：6 months
|
Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.
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6 months
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Quality of Life Survey (QoL) - Treatment Satisfaction
大体时间：6 months
|
Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
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6 months
|
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Quality of Life Survey (QoL) - Treatment Impact
大体时间：6 months
|
Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
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6 months
|
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Quality of Life Survey (QoL) - Social or Vocational Worry
大体时间：6 months
|
Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.
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6 months
|
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Quality of Life Survey (QoL) - Hypoglycemia Fear
大体时间：6 months
|
Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry.
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6 months
|
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Quality of Life Survey (QoL) - Glycemia Control Perception
大体时间：6 months
|
Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.
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6 months
|
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Quality of Life Survey (QoL) - Lifestyle Flexibility
大体时间：6 months
|
Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.
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6 months
|
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Quality of Life Survey (QoL) - Social Stigma
大体时间：6 months
|
Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.
|
6 months
|
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Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment
大体时间：6 months
|
Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.
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6 months
|
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Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment
大体时间：6 months
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Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.
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6 months
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540.
- Vanderheiden A, Harrison LB, Warshauer JT, Adams-Huet B, Li X, Yuan Q, Hulsey K, Dimitrov I, Yokoo T, Jaster AW, Pinho DF, Pedrosa I, Lenkinski RE, Pop LM, Lingvay I. Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin. J Clin Endocrinol Metab. 2016 Apr;101(4):1798-806. doi: 10.1210/jc.2015-3906. Epub 2016 Feb 24.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2012年1月1日
初级完成 (实际的)
2016年6月1日
研究完成 (实际的)
2016年6月1日
研究注册日期
首次提交
2012年1月4日
首先提交符合 QC 标准的
2012年1月5日
首次发布 (估计)
2012年1月6日
研究记录更新
最后更新发布 (实际的)
2018年1月16日
上次提交的符合 QC 标准的更新
2017年12月15日
最后验证
2017年12月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.