Magnetic Resonance Assessment of Victoza Efficacy in the Regression of Cardiovascular Dysfunction In Type 2 Diabetes Mellitus and South Asian Descent
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Peak ejection rate
研究概览
简要总结
Among South Asians, in comparison to Western Europeans, there is an increased risk of type 2 diabetes mellitus (DM2) and DM2-related cardiovascular disease. The effect of Liraglutide (Victoza®) on cardiovascular function is therefore investigated in the DM2 patient group of South Asian descent specifically.
Liraglutide is a new widely prescribed therapeutic agent for DM2 patients. It is a Glucagon Like Peptide - 1 homologue that improves glucose homeostasis and reduces blood pressure and body weight. The disadvantageous metabolic phenotype as seen in South Asians includes a relatively large total fat mass, with predominately visceral relative to subcutaneous adipose tissue and lower brown adipose tissue volume and activity, accompanied by increased lipid levels. The key elements in the mechanism of action of Liraglutide seem to correspond to the differences in metabolic profile between South Asians and Western Europeans. Diastolic dysfunction, an early finding of cardiovascular disease in DM2 and obesity and an independent predictor of mortality, has been shown to be associated with the amount of triglyceride accumulation in the heart and liver. The investigators hypothesize that Liraglutide has direct advantageous cardiovascular effects and reduces triglyceride accumulation in end-organs, specifically for DM2 patients of South Asian descent.
详细描述
RECRUITMENT AND SCREENING PROCEDURE OF STUDY POPULATION
Patients will be recruited from the outpatient clinics of the Leiden University Medical Center, general practitioners, local hospitals and by advertisement. Patients own physicists will be asked to point eligible patients to the opportunity of study participation. If interested, patients will be informed by the principal investigator. The screening will consist of a medical history, physical examination consisting of measurement of height, body weight, heart rate, blood pressure and examination of thorax and abdomen. Furthermore laboratory tests and rest-ECG will be performed. If the patient is eligible and willing to participate in the study, and has signed the informed consent, the patient will be included. Informed consent must be obtained before any trial related activities take place. After inclusion in the study protocol, the patient's treating physician and general practitioner will be notified.
SAMPLE SIZE CALCULATION
Clinically relevant differences and standard deviations of two studies were chosen to generate data for the sample size calculation. The data we used to incorporate the precision of MRI assessment of cardiac function was generated by a study performed by our group with pioglitazone vs metformin on cardiac function parameters. To estimate the effect of GLP-1 therapy on cardiac function, we only have data of a pilot study with eight DM2 patients with heart failure. With a power of 90% and alfa = 0.05, groups varying from 9 to 17 patients will be needed. In a comparable trial the drop-out rate was 10%. Taken into consideration that the population studied will have a significant better systolic function than the heart failure patients studied by Sokos et al, differences may be smaller. In conclusion, investigators estimate to be able to detect a clinically relevant, significant result with 90% power and alfa = 0.05 with 25 patients in each group.
USE OF CO-INTERVENTION
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
- 19 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent
- •Age > 18 years and < 75 years
- •BMI > 23 kg/m2
- •DM2 treated with metformin and/or SU derivative and/or insulin for at least 3 months in stable dosage
- •HbA1c ≥ 6.5% and ≤ 11.0% (≥ 47.5 mmol/mol and ≤ 97.4 mmol/mol)
- •EGFR > 30 ml/min
- •Ethnicity: South Asian descent (i.e. Hindustani Surinamese), based on self-identified ethnicity and self-reported origin of the mother, the father and the mother's and father's ancestors. Both parents and the mother's and father's ancestors should be South Asian for inclusion.
排除标准
- •Use of thiazolidinediones (TZD), GLP-1 analogues, DPP-IV inhibitors, fibrates, prednisone, cytostatic or antiretroviral therapy within 6 months prior to the study
- •Uncontrolled treated or untreated hypertension (systolic blood pressue ≥ 180 mmHg and/or diastolic blood pressue ≥ 110 mmHg)
- •Acute coronary or cerebrovascular event within 30 days prior to study
- •Congestive heart failure NYHA III-IV
- •Hereditary lipoprotein disease
- •Psychiatric disorders and / or use of antipsychotic or antidepressant drugs at present or in the past
- •Hepatic disease (AST/ALT > 2 times reference values)
- •Endocrine disease other than diabetes mellitus type 2
- •Any significant chronic disease (e.g. inflammatory bowel disease)
- •Any significant abnormal laboratory results found during the medical screening procedure
- •Gastrointestinal surgery (e.g. gastric bypass)
- •Pregnant woman or a woman who is breast-feeding
- •Female of child-bearing potential intending to become pregnant or is not using adequate contraceptive methods while sexually active
- •Allergy to intravenous contrast
- •Known or suspected hypersensitivity to trial products or related products
- •Chronic pancreatitis or previous acute pancreatitis
- •Personal history or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia type 2
- •Claustrophobia
- •Metal implants or other contraindications for MRI
- •Recent participation in other research projects within the last 3 months or participation in 2 or more projects in one year
研究组 & 干预措施
Liraglutide
Liraglutide: Solution for subcutaneous injection 6 mg/ml; Flexpen 3 ml.
Dose: s.c. 0,6 mg (0,1 mL) once daily. After 1 week, the dose will be increased to 1,2 mg (0,2 mL) once daily. If tolerated, after 1 week, dose will be increased to 1.8 mg (0,3 mL) once daily. In case of a hypoglycaemic episode, the dosage of oral blood glucose lowering medicaments will be adjusted first. If hypoglycaemia persists, Liraglutide / Liraglutide placebo will be adjusted on the basis of clinical parameters.
Duration: 26 weeks
干预措施: Liraglutide (Drug)
Liraglutide - Placebo
Liraglutide placebo: Solution for injection; Flexpen 3 ml.
Dose: same as Liraglutide
Duration: 26 weeks
干预措施: Liraglutide - Placebo (Drug)
结局指标
主要结局
Peak ejection rate
时间窗: 0 and 26 weeks
Change from baseline in ml end-diastolic volume/sec: difference between groups
Early peak filling rate
时间窗: 0 and 26 weeks
Change from baseline in ml end-diastolic volume/sec: difference between groups
Early deceleration peak
时间窗: 0 and 26 weeks
Change from baseline in ml/sec: difference between groups
Atrial peak filling rate
时间窗: 0 and 26 weeks
Change from baseline in ml/sec: difference between groups
Early deceleration peak / Atrial peak filling rate (E/A ratio)
时间窗: 0 and 26 weeks
Change from baseline of the ratio: difference between groups
Peak mitral annulus longitudinal motion
时间窗: 0 and 26 weeks
Change from baseline in cm/sec: difference between groups
Stroke volume
时间窗: 0 and 26 weeks
Change from baseline in ml: difference between groups
Ejection Fraction
时间窗: 0 and 26 weeks
Change from baseline in percentage: difference between groups
Cardiac output
时间窗: 0 and 26 weeks
Change from baseline in L/min: difference between groups
Cardiac index
时间窗: 0 and 26 weeks
Change from baseline in L/min/m2: difference between groups
Left ventricular filling pressure (= early peak filling rate / peak mitral annulus longitudinal motion)
时间窗: 0 and 26 weeks
Change from baseline in mmHg: difference between groups
次要结局
- Aorta vessel wall imaging(0 and 26 weeks)
- Carotid vessel wall imaging(0 and 26 weeks)
- Adipose tissue distribution(0 and 26 weeks)
- Total body fat(0 and 26 weeks)
- Epicardial fat volume(0 and 26 weeks)
- Magnetic Resonance Spectroscopy of the heart(0 and 26 weeks)
- Magnetic Resonance Spectroscopy of the liver(0 and 26 weeks)
- Magnetic Resonance Spectroscopy of the kidney(0 and 26 weeks)
- HBA1C(Time Frame: 0,8, 12, 16 and 26 weeks)
- Fasting blood glucose level(0, 4, 8, 12, 16, 20, 26 weeks)
- Myocardial T1 - mapping(0 and 26 weeks)
- Brown adipose tissue(0 and 26 weeks)
研究者
MalouPaiman
MD
Leiden University Medical Center