Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early Diabetes (RELEASE)
Diabetes is associated with an increased risk for developing premature macrovascular complications. The process of irreversible subclinical damage to the vasculature already starts during its preceding stages. Dipeptidyl peptidase (DPP)-4 inhibitors have been shown to attenuate vascular damage in preclinical studies. Off-target effects on adipose tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in animal studies.
Based on these considerations the investigators hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with treatment naive type 2 diabetes will lead to beneficial effects on arterial stiffness as measured by pulse wave velocity.
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Groningen、荷兰、9700 RB
- University Medical Center Groningen
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Men and women, age 30 to 70 years, AND
- Treatment naïve type 2 diabetes, as defined as t
- Fasting plasma glucose ≥ 7.0 mmol/l, OR
- Random plasma glucose ≥ 11.1 mmol/l, OR
- HbA1c ≥6,5%
- Written informed consent
- Assessable Pulse Wave Velocity measurement at screening
Exclusion Criteria:
- Current or previous use of glycemic control medications
- Type 1 diabetes
- Gestational diabetes mellitus
- Other specific types of diabetes due to other causes, e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation)
- Uncontrolled hypertension, defined as systolic blood pressure >160 or a diastolic blood pressure >100 mmHg at screening visit
- Severe dyslipidemia indicating primary dyslipidemia, defined as total cholesterol >8 mmol/l, triglycerides >10 mmol/l of high density lipoprotein cholesterol <0.6 mmol/l
- Current use of weight loss medication or previous weight loss surgery
- History of severe gastrointestinal disease
- Clinical contraindications to DPP4-inhibitors
- Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease
- Symptomatic heart failure, New York Heart Association (NYHA) class II-IV
- Women who are currently pregnant,planning to become pregnant,breastfeeding women, or women with child bearing potential not using appropriate contraceptive measures
- Clinically significant liver disease or hepatic function greater than 3 times upper limit of normal
- Known impaired renal function or eGFR <30 ml/min/1.73m2
- Patients who are mentally incompetent and cannot sign a Patient Informed Consent
- Current active malignancy or in the previous 6 months
- Documented HIV infection
- Use of rifampicin
学习计划
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:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Linagliptin
Linagliptin 5 mg/day + lifestyle advise
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one tablet linagliptin 5 mg/day for 26 weeks
其他名称:
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安慰剂比较:Placebo
Matching placebo + lifestyle advise
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one tablet matching placebo/day for 26 weeks
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
大体时间:baseline, week 26
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baseline, week 26
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Secondary vascular study parameters
大体时间:baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Subclinical vascular inflammation (FDG PET-CT)
大体时间:26 weeks
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Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography coregistration (FDG PET-CT)
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26 weeks
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Body Mass Index and Waist-to-Hip ratio
大体时间:baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Body Mass Index and Waist-to-Hip ratio
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Blood pressure
大体时间:baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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24-hours ambulatory blood pressure measurement (24-ABPM)
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Advanced glycation end products
大体时间:baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Skin AGE deposition measured and plasma levels of AGEs
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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plasma markers of inflammation
大体时间:baseline, week 26
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baseline, week 26
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plasma markers of endothelial dysfunction
大体时间:baseline, week 26
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baseline, week 26
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Glycemic indices
大体时间:baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Fasting glucose (FPG) and 2-hour post OGTT glucose (OGTT), HbA1c
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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albuminuria
大体时间:baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Urinary albumin/creatinine ratio
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Lifestyle
大体时间:baseline, week 26
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Intake of energy, Eating behaviour, and Physical activity
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baseline, week 26
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合作者和调查者
调查人员
- 首席研究员:Pieter W Kamphuisen, MD PhD、University Medical Center Groningen
出版物和有用的链接
一般刊物
- Reijrink M, de Boer SA, Spoor DS, Lefrandt JD, Lambers Heerspink HJ, Boellaard R, Greuter MJ, Borra RJH, Hillebrands JL, Slart RHJA, Mulder DJ. Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors. Atherosclerosis. 2019 Nov;290:87-93. doi: 10.1016/j.atherosclerosis.2019.09.016. Epub 2019 Sep 25.
- de Boer SA, Hovinga-de Boer MC, Heerspink HJ, Lefrandt JD, van Roon AM, Lutgers HL, Glaudemans AW, Kamphuisen PW, Slart RH, Mulder DJ. Arterial Stiffness Is Positively Associated With 18F-fluorodeoxyglucose Positron Emission Tomography-Assessed Subclinical Vascular Inflammation in People With Early Type 2 Diabetes. Diabetes Care. 2016 Aug;39(8):1440-7. doi: 10.2337/dc16-0327. Epub 2016 Jun 8.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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Linagliptin的临床试验
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Boehringer IngelheimEli Lilly and Company完全的