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

• 批准号: 8212573
• 负责人: Susan Hedayati
• 金额: $ 34.52万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212573
• 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; Clinical Trials Design; 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; public health relevance; randomized trial; single episode major depressive disorder; week trial

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）：抑郁症在透析患者中​​很常见，是住院和死亡的独立危险因素。我实验室的最新研究表明，未接受透析的慢性肾病 (CKD) 患者中约有 20% 患有重度抑郁发作 (MDE)，且一年内住院、开始透析或死亡的可能性是未接受透析的患者的两倍对于那些没有 MDE 的人。然而，只有少数患有抑郁症的 CKD 患者接受了抗抑郁药物治疗。慢性肾病患者治疗率低的一个主要原因是缺乏支持抗抑郁药对慢性肾病患者的疗效和安全性的研究。舍曲林抗抑郁性心脏病随机试验显示，血清素选择性再摄取抑制剂 (SSRI) 舍曲林对心血管结局有益，但排除了中度至重度 CKD 患者。鉴于 CKD 患者心血管 (CV) 死亡率过高，有必要研究抑郁症治疗对这些患者是否安全有效。需要这些信息来设计结果试验，以确定抑郁症治疗是否可以挽救该人群的生命并提高生活质量。在本申请中，我提出了一项初步研究，以检验以下假设：用舍曲林短期治疗 MDE 将改善透析前 3b-5 期 CKD 患者的抑郁症状严重程度和生活质量。我进一步假设，用舍曲林治疗 MDE 对于这些患者来说是安全且耐受性良好的。本研究的目的是 1) 确定与安慰剂相比，舍曲林治疗是否能改善抑郁症状的严重程度以及整体功能和生活质量。我将使用一项随机、双盲、安慰剂对照的灵活剂量 12 周试验，涉及 200 名透析前 3-5 期 CKD 受试者；并分别评估工作和社会适应量表以及肾脏疾病生活质量调查（KDQOL-SF）； 2) 确定舍曲林与安慰剂相比是否具有耐受性和安全性。这将通过 a) 每组中发生严重不良事件（包括需要输血或住院的出血）的比例来评估； b) 治疗紧急效应系统评估量表中报告的副作用的类型和严重程度； c) 根据副作用频率、强度和负担评定量表报告的副作用在每组中的比例； d) 与安慰剂组相比，舍曲林的血小板聚集和活化相对于基线的减少，以及这种减少是否与较高的血浆舍曲林水平相关； 3) 在探索性分析中，我还将通过评估以下方面的变化来研究舍曲林可能影响结果的机制：a) 营养状况； b) 遵守处方药物； c) 认知功能； d) 炎症标志物；我还将收集随机分组后 6 个月和 12 个月时的死亡、住院和透析开始数据。后者的信息将用于功效计算，以确定进行大规模试验的可行性，以调查抑郁症治疗是否可以改善 CKD 的预后。