Targeting Peroxisome Proliferator-Activated Receptor-Gamma in Peritoneal Dialysis Patients - Will it Reduce Inflammation, Atherosclerosis, Calcification and Improve Survival of Peritoneal Dialysis Patients? (PROOF Trial)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Change in carotid intima-media thickness
研究概览
简要总结
To study whether peroxisome proliferator-activated receptor-gamma activation in peritoneal dialysis patients will reduce inflammation, atherosclerosis, calcification and improve survival of peritoneal dialysis patients
详细描述
Peritoneal dialysis patients are at increased risk of cardiovascular morbidity and mortality and are related to the presence of accelerated atherosclerosis. Other than the traditional cardiovascular risk factors, there is increasing evidence that inflammation is associated with the development of atherosclerosis and cardiovascular events in both the general and dialysis population. C-reactive protein is predictive of higher all-cause mortality and cardiovascular mortality, independent of other cardiovascular risk factors and atherosclerotic vascular disease. As a considerable proportion of peritoneal dialysis patients showed elevated C-reactive protein, it raises an important question as to whether lowering C-reactive protein will have any cardiovascular and survival benefit in these patients. On the other hand, insulin resistance with associated hyperinsulinemia is frequently observed in chronic renal failure and dialysis patients. Although the exact mechanism of insulin resistance needs further evaluation, studies indicated that insulin resistance is an important cardiovascular risk factor and outcome predictor in the general and dialysis population. Moreover, recent evidence indicates an association between chronic inflammation and insulin resistance although the exact interrelationship remains unclear. The peroxisome proliferator-activated receptor-gamma (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. PPAR-g is highly expressed in adipose tissue and clinical study has confirmed efficacy of the specific ligands for PPAR-gamma, namely thiazolidinediones (TZD), in improving insulin sensitivity. Recent experimental and clinical studies demonstrated that TZD has anti-inflammatory and anti-atherosclerotic properties other than insulin sensitizing effect in type 2 diabetics. We hypothesize that modulation of the PPAR-g activity may be a novel therapeutic strategy for reducing inflammation and improving insulin sensitivity and may retard the progression of atherosclerosis and possibly reduce mortality of our peritoneal dialysis patients.
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)
盲法说明
Double-blind randomized placebo-controlled trial, all parties are masked
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Both prevalent patients or patients newly started on continuous peritoneal dialysis, with or without diabetes mellitus will be considered eligible for study entry.
- •For patients newly started on chronic peritoneal dialysis, they will be suitable for recruitment into the study after one month on peritoneal dialysis.
- •Patients who provide informed consent for the study
排除标准
- •Patients with underlying active malignancy
- •Patients with chronic liver disease or liver cirrhosis
- •Patients with active infections
- •Patients with other chronic active inflammatory disease such as systemic lupus erythematosus, rheumatoid arthritis
- •Patients who refuse study participation
- •Patients with underlying congenital heart disease or rheumatic heart disease
- •Patients with poor general condition
- •Patients with plans for living related kidney transplant within 2 years
- •Female patients with pregnancy
- •Patients with history of recurrent hypoglycemia
- •Patients with Class III and IV congestive heart failure
- •Patients already receiving glitazones treatment at the screening visit
研究组 & 干预措施
Active intervention arm
Peroxisome proliferator activator receptor gamma treatment, Pioglitazone
干预措施: Pioglitazone (Drug)
placebo pill
placebo comparator
干预措施: placebo comparator (Drug)
结局指标
主要结局
Change in carotid intima-media thickness
时间窗: over 48 weeks
Change in carotid intima-media thickness
change in flow mediated dilatation (marker of endothelial function)
时间窗: over 48 weeks
change in flow mediated dilatation (marker of endothelial function)
次要结局
- Change in central diastolic blood pressure(over 96 weeks)
- change in abdominal visceral fat(over 96 weeks)
- change in D/P creatinine ratio(over 96 weeks)
- change in heart valves calcium score(over 96 weeks)
- change in carotid artery calcium score(over 96 weeks)
- change in C-reactive protein(over 96 weeks)
- change in residual kidney function(over 96 weeks)
- change in peritoneal ultrafiltration with 2.5% during PET(over 96 weeks)
- change in aortic pulse wave velocity(over 96 weeks)
- change in nitroglycerin-mediated dilatation(over 48 weeks)
- change in coronary artery calcium score(over 96 weeks)
- change in insulin dose (among those on insulin)(over 96 weeks)
- change in augmentation index-heart rate adjusted(over 96 weeks)
- change in subcutaneous fat(over 96 weeks)
- change in blood pressure(over 96 weeks)
- change in handgrip strength(over 96 weeks)
- change in endothelial progenitor cells(over 96 weeks)
- change in central systolic blood pressure(over 96 weeks)
- change in HOMA index (among those not on insulin)(over 96 weeks)
- Change in cardiac biomarkers(over 96 weeks)
- change in glycemic control (fasting glucose, and glycosylated hemoglobin)(over 96 weeks)
研究者
Dr. Angela Yee-Moon Wang
Dr.
The University of Hong Kong