MB001-067 A PROSPECTIVE, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, RANDOMIZED TRIAL OF EXTENDED RELEASE EXENATIDE VERSUS PLACEBO (COHORT A) AND A PROSPECTIVE, SINGLE GROUP, OPEN-LABEL, BLINDED OUTCOME TRIAL OF EXTENDED RELEASE EXENATIDE (COHORT B) IN DIABETIC PATIENTS WITH TYPE 4 CARDIORENAL SYNDROME (EXTEND-CRS TRIAL) AMENDMENT 3
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- ST2
研究概览
简要总结
Among adult individuals with type 2 diabetes mellitus and at risk for heart failure with impaired relaxation of the heart mildly reduced kidney filtration function (Type 4 cardiorenal syndrome) this trial will evaluate the quantitative impact of 38 weeks of treatment with exenatide extended-release injections versus placebo. on a cardiac biomarker blood test score, cardiac fibrosis seen on magnetic resonance scanning, cardiac strain identified by ultrasonography and strain rate imaging, and a kidney urine biomarker score.
详细描述
Primary Aim
Among adult individuals with type 2 diabetes mellitus (T2DM) and at risk for diastolic heart failure (DHF) and mildly reduced renal filtration function (Type 4 cardiorenal syndrome), to evaluate the quantitative impact on the MISS (myocardial injury summary score) cardiac biomarker score, cardiac fibrosis by MRI, cardiac strain by ultrasonography and strain rate imaging, and KISS (kidney injury summary score) kidney biomarker score after 38 weeks of treatment with exenatide extended-release or placebo.
Secondary Aim
To evaluate the inter-relationships between demographic, clinical, and biochemical variables (MISS score, KISS score) and of progressive cardiac fibrosis as assessed by MRI, strain-rate imaging, and in adult individuals with T2DM and at risk for DHF (Type 4 cardiorenal syndrome).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes mellitus with hemoglobin A1C 6.6-9.9% with or without the use of insulin
- •Estimated glomerular filtration rate (eGFR) between 50 and 90 ml/min/1.73 m2
排除标准
- •Allergy or intolerance to gadolinium
- •Implanted cardiac pacemaker, defibrillator, loop recorder, or other implanted metallic device
- •Any other metallic implanted device that is a contra-indication to MRI scanning
- •eGFR < 50 ml/min/1.73 m2
- •eGFR > 90 ml/min/1.73 m2
- •Patient has ever been treated with an approved or investigational GLP-1 receptor agonist e.g. BYETTA™ (exenatide), BYDUREON™ (Exenatide extended-release), VICTOZA™ (liraglutide), or taspoglutide
- •Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial.
- •Disorders of iron metabolism
- •Collagen vascular diseases
- •Myocardial infarction
- •Use of DDP4 inhibitors, and PPAR gamma agonists
- •Pregnancy or planned pregnancy during the trial period
- •Hemoglobin A1C of ≥ 10.0% or <6.6%
- •Fasting glucose ≥ 260 mg/dl
- •Clinically significant abnormal baseline laboratories
- •Morbid obesity or body girth that prohibits the ability to undergo echocardiography or MRI scanning with high-quality image results
- •Renal transplantation
- •Severe gastrointestinal, liver, or neurodegenerative disease
- •Decompensated liver cirrhosis (Child-Pugh score >7)
- •New York Heart Association Class III or IV heart failure
- •Patients have alanine aminotransaminase (ALT) greater than 5 times the upper limit of the reference range.
- •Prior pancreatitis
- •Personal or family history of medullary thyroid adenoma or carcinoma (MTC)
- •Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- •History of severe hypoglycemia
- •Prior bariatric surgery
研究组 & 干预措施
Exenatide-extended release
Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks
干预措施: BYDUREON (Drug)
Placebo
Matching placebo subcutaneously once per week x 38 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
ST2
时间窗: 38 weeks
Mean change in plasma ST2 (pg/ml)
Galectin-3
时间窗: 38 weeks
Mean change in plasma galectin-3 (pg/ml)
L-FABP
时间窗: 38 weeks
Mean change in urine L-type fatty acid binding protein:Cr ratio
NGAL
时间窗: 38 weeks
Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio
KIM-1
时间窗: 38 weeks
Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio
NAG
时间窗: 38 weeks
Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio
Cystatin-C
时间窗: 38 weeks
Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)
IL-18
时间窗: 38 weeks
Mean change in urine interleukin-18:Cr ratio
Troponin I
时间窗: 38 weeks
Mean change in plasma ultrasensitive troponin I (pg/ml)
Pi GST
时间窗: 38 weeks
Mean change in pi glutathione S-transferase (piGST):Cr ratio
BNP
时间窗: 38 weeks
Mean change in plasma B-type natriuretic peptide BNP (pg/ml)
ACR
时间窗: 38 weeks
Mean change in urine albumin:Cr ratio (ACR)
Alpha GST
时间窗: 38 weeks
Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio
次要结局
未报告次要终点