Randomized trial of sertraline treatment of depression in Chronic Kidney Disease

舍曲林治疗慢性肾脏病抑郁症的随机试验

基本信息

批准号：
8792383
负责人：
Susan Hedayati
金额：
$ 34.58万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8792383
关键词：
Adherence Adverse effects Affect Anemia Angiotensin-Converting Enzyme Inhibitors Antidepressive Agents Antihypertensive Agents Blood Platelets Blood Transfusion Cardiovascular system Cessation of life Chronic Kidney Failure Comorbidity Data Diabetes Mellitus Diagnosis Dialysis procedure Dose Double-Blind Method Dyslipidemias Ensure Frequencies Future Hemorrhage High Prevalence Hospitalization Hypertension Impaired cognition Intervention Kidney Kidney Diseases Laboratories Lead Maintenance Major Depressive Disorder Medical Mental Depression Minority Morbidity - disease rate Myocardial Infarction Nutritional status Outcome Patients Pharmaceutical Preparations Pilot Projects Placebo Control Placebos Plasma Platelet Activation Platelet aggregation Population Public Health Publishing Qualifying Quality of life Randomized Recruitment Activity Reporting Research Research Personnel Risk Factors Safety Secondary Hyperparathyroidism Selective Serotonin Reuptake Inhibitor Serious Adverse Event Sertraline Severities Severity of illness Side Social Adjustment Staging Surveys Testing Time Work cardiovascular risk factor cognitive function depressive symptoms design flexibility high risk improved inflammatory marker inventory of depressive symptomatology mortality patient population primary outcome randomized trial single episode major depressive disorder trial design week trial

项目摘要

DESCRIPTION (provided by applicant): Depression is common in those on dialysis and is an independent risk factor for hospitalization and death. Recent studies from my laboratory have shown that about 20% of patients with chronic kidney disease (CKD) not on dialysis suffer from a major depressive episode (MDE) and are twice as likely to be hospitalized, initiate dialysis or die within a year as compared to those without a MDE. However, only a minority of CKD patients with depression are treated with antidepressants. A major reason for low treatment rates in those with CKD is lack of studies that support the efficacy and safety of antidepressants in CKD patients. The Sertraline AntiDepressant Heart Attack Randomized Trial showed benefit of serotonin-selective reuptake inhibitor (SSRI) sertraline on cardiovascular outcomes but excluded patients with moderate to severe CKD. Given the excessive rates of cardiovascular (CV) death in CKD patients, it becomes imperative to investigate whether treatment of depression is safe and efficacious in these patients. This information is needed to design an outcomes trial to determine if treatment of depression saves lives and improves quality of life in this population. In this application, I propose a pilot study to test the hypothesis that short-term treatment of a MDE with sertraline will result in improvement in depression symptom severity and quality of life in patients with predialysis stages 3b-5 CKD. I further hypothesize that treatment of MDE with sertraline is safe and well- tolerated in these patients. The aims of this study are to 1) determine if treatment with sertraline, as compared with placebo, results in an improvement in depression symptom severity and overall function and quality of life. I will use a randomized, double-blinded, placebo-controlled flexible-dose 12-week trial involving 200 subjects with predialysis stages 3-5 CKD; and assess the Work and Social Adjustment Scale and Kidney Disease Quality of Life Survey (KDQOL-SF), respectively; 2) determine if sertraline, as compared with placebo, is tolerable and safe. This will be assessed by a) proportion in each group with serious adverse events including bleeding requiring blood transfusion or hospitalization; b) type and severity of side effects reported on the Systemic Assessment for Treatment Emergent Effects scale; c) proportion in each group with side effects reported on the Frequency, Intensity and Burden of Side Effects Rating scale; d) reduction in platelet aggregation and activation from baseline in the sertraline as compared with placebo group, and whether this reduction correlates with higher plasma sertraline levels; 3) In exploratory analyses, I will also investigate mechanisms by which sertraline may affect outcomes by evaluating change in: a) nutritional status; b) adherence to prescribed medications; c) cognitive functioning; and d) markers of inflammation; I will also collect data on death, hospitalizations, and dialysis initiation at 6 and 12 months after randomization. The latter information will be used for power calculations to determine the feasibility of conducting a large-scale trial to investigate whether treatment of depression improves outcomes in CKD.

描述（由申请人提供）：抑郁症在透析中很常见，是住院和死亡的独立危险因素。我的实验室的最新研究表明，与没有MDE相比，约有20％的慢性肾脏疾病患者（CKD）不患有严重的抑郁发作（MDE）（MDE），并且在一年内住院或在一年内死亡的可能性是两倍。但是，只有少数CKD抑郁症患者接受抗抑郁药治疗。 CKD患者的治疗率低的主要原因是缺乏支持CKD患者抗抑郁药的功效和安全性的研究。舍曲雷林抗抑郁药随机试验显示5-羟色胺选择性再摄取抑制剂（SSRI）在心血管结局上的好处，但排除了中度至重度CKD的患者。鉴于CKD患者的心血管（CV）死亡率过高，因此必须研究这些患者的抑郁症治疗是否安全有效。需要此信息来设计结果试验，以确定抑郁症的治疗是否可以挽救生命并改善该人群的生活质量。在此应用中，我提出了一项试点研究，以检验以下假设：舍曲林的短期治疗将导致抑郁症状的严重程度和抑郁症症状严重程度和生活质量的改善。我进一步假设，在这些患者中，用舍曲林治疗MDE是安全且耐受性的。这项研究的目的是1）确定与安慰剂相比，用舍曲林治疗是否会改善抑郁症状严重程度以及整体功能和生活质量。我将使用一个随机，双盲的，安慰剂对照的柔性剂量为12周的试验，涉及200名受试者3-5 CKD的受试者；并分别评估工作和社会调整量表和肾脏疾病生活质量调查（KDQOL-SF）； 2）确定与安慰剂相比，舍曲林是否可以忍受且安全。这将通过a）每组的比例进行评估，包括严重的不良事件，包括流血或住院的出血； b）报告的副作用的类型和严重程度报告了治疗效果量表的全身评估； c）每组的比例，并报告了副作用评级量表的频率，强度和负担； d）与安慰剂组相比，舍曲林的基线的血小板聚集和激活减少，以及这种还原是否与较高的血浆舍曲林水平相关； 3）在探索性分析中，我还将调查舍曲林通过评估变化来影响结果的机制：a）营养状况； b）遵守处方药； c）认知功能； d）炎症的标记；我还将在随机分组后6到12个月收集有关死亡，住院和透析起步的数据。后一个信息将用于电源计算，以确定进行大规模试验以调查抑郁症治疗的可行性是否可以改善CKD的结局。