Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Change in LV Mass
研究概览
简要总结
Heart failure (HF) is an epidemic and is a major burden on the US healthcare system. The most common cardiovascular endpoint is HF. Thus, novel interventions to prevent HF in chronic kidney disease (CKD) are highly desirable. This study will assess: the variability in the response to isosorbide mononitrate (ISMN) therapy; the degree of change in central hemodynamics and cardiac endpoints through analysis of changes in left ventricle (LV) mass, diffuse myocardial fibrosis, and myocardial systolic and diastolic function.
详细描述
This is a open label, parallel arm, randomized study of ISMN with or without vitamin C to improve exercise capacity and LV remodeling in CKD. Twenty subjects with CKD will be enrolled in this study and three different daily doses of sustained release isosorbide mononitrate (SR-ISMN) will be administered over time accompanied by a random administration of vitamin C in half of the subjects (500 mg three times daily). Before administration of SR-ISMN, baseline assessments will be performed. These include arterial tonometry, Doppler echocardiography, reflection magnitude measurements, a bicycle exercise test, activity monitoring, cardiac MRI, 24-hour blood pressure monitoring, and blood drawing. After these assessments, a dose of 30 mg of SR-ISMN will be administered daily (either with or without vitamin C) for the first week, 60 mg SR-ISMN for the second week, and 120 mg for the third week. After each week, blood pressure and central hemodynamics will be assessed. The third week visit also includes the bicycle exercise study and initiating the long term dose (60 or 120 mg) of SR-ISMN. In the long-term phase, blood pressure and hemodynamics are assessed at 12-weeks post initiation of the study medication(s). After 24 weeks we will perform the final assessment, which includes the same tests performed during the baseline assessment. Enrollment will take place at the Hospital of the University of Pennsylvania and the Penn Presbyterian Medical Center.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •Chronic kidney disease stage 3
- •Elevated left ventricular mass index or LV posterior wall thickness >1.4 cm documented in a clinically indicated echocardiographic or MRI examination within the previous 24 months or electrocardiographic LV hypertrophy
- •Stable medical therapy as defined by no addition, removal or change in dosage >100% of Angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, or calcium channel blockers for > 30 days
- •Current therapy with an ACE inhibitor, hydralazine or a statin, all of which have been shown to reduce nitrate tolerance
排除标准
- •A clinically- indicated stress test demonstrating significant myocardial ischemia within 1 year of enrollment, not followed by coronary revascularization
- •Rhythm other than sinus (i.e., atrial fibrillation)
- •Non-cardiac condition limiting life expectancy to <1 year
- •Current or anticipated future need for long acting organic nitrate therapy
- •Severe aortic or mitral valve disease
- •Hypertrophic cardiomyopathy
- •Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid)
- •Pericardial disease
- •Primary pulmonary arteriopathy
- •History of myocardial infarction, unstable angina, percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days, or requirement for either PTCA or CABG at the time of consent
- •Resting heart rate (HR) >100 bpm
- •A reduced LV ejection fraction (EF<50%)
- •Known severe liver disease (AST >3x normal, alkaline phosphatase or bilirubin >2x normal)
- •Allergy to ISMN
- •Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardanafil or tadalafil
- •Therapy with rosiglitazone
- •Current pregnancy or a positive urine pregnancy test; women who become pregnant during the study will be discontinued from the trial
- •Therapy with warfarin
- •History of kidney stones
- •History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •Systolic blood pressure <110 mmHg or diastolic blood pressure <40 mmHg;
- •Contraindications to a cardiac MRI: (a) Central nervous system aneurysm clips; (b) Implanted neural stimulators; (c) Implanted cardiac pacemaker or defibrillator; (d) Cochlear implant; (e) Ocular foreign body (e.g. metal shavings); (f) Other implanted medical devices: (e.g. drug infusion ports); (g) Insulin pump; (h) Metal shrapnel or bullet; (i) Claustrophobia; (j) Extreme obesity rendering the patient unable to fit into narrow-bore scanners; (k) Unwillingness of the patient to undergo a cardiac MRI.
研究组 & 干预措施
ISMN Only
Patients receive only ISMN
干预措施: ISMN (Drug)
ISMN AND Vitamin C
Patients receive both ISMN and Vitamin C
干预措施: ISMN (Drug)
ISMN AND Vitamin C
Patients receive both ISMN and Vitamin C
干预措施: Vitamin C (Dietary Supplement)
结局指标
主要结局
Change in LV Mass
时间窗: Measured at Baseline Visit and 24 Week Visit
Variability seen in change in LV mass with ISMN administration measured with steady-state free precession cardiac MRI, outcomes reflect the change, in grams
次要结局
- Changes in Myocardial Systolic and Diastolic Function(Measured at Baseline Visit and 24 visits)
- Changes in Diffuse Myocardial Fibrosis(Measured at Baseline Visit and 24 Week Visit)
- Pulse Wave Reflection Magnitude(Measured between Baseline Visit-Week 24)
- Aerobic Capacity(Change from Baseline at Week 24 reported)
研究者
Julio A. Chirinos
Principal Investigator
University of Pennsylvania