Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)

项目摘要 我们研究的总体目标是确定是否治疗严重抑郁障碍(MDD)。 改善慢性肾脏疾病(CKD)患者的预后。我们发现MDD存在于多达 25%的CKD患者与CKD进展到终末期肾脏疾病独立相关， 住院和死亡。研究还表明，抑郁与以患者为中心的不良结局有关。 例如较低的生活质量(QOL)、疲劳、睡眠不佳以及不坚持饮食和药物治疗。然而， 常用抗抑郁药物或非药物的有效性和耐受性证据 CKD患者的治疗非常有限。之前的数据主要来自依赖透析的患者， 受制于小样本、缺乏随机化和对照、持续时间短和高辍学率。我们的 该小组是第一个对201名患者进行MDD治疗的双盲随机对照试验 研究表明，舍曲林是一种常用的选择性5-羟色胺再摄取抑制剂(SSRI)， 在改善抑郁症状方面并不比安慰剂有效。鉴于MDD的高流行率 在慢性肾脏病中，其与不良结局的相关性，以及缺乏支持常规药物疗效的数据 随着治疗的深入，测试治疗慢性肾脏病患者MDD的新策略变得势在必行。我们建议 与对照组相比，两种新的治疗策略的有效性和耐受性-(1)行为 激活远程治疗(BAT)16周，在8岁时加入安非他酮，一种非SSRI抗抑郁药 (2)安非他酮治疗16周，与 对于不汇款的人，在8周内增加BAT。在目标1中，我们将研究这两种药物的疗效和耐受性。 201例患者抑郁症状主要终点改善的策略与对照(67% 组)非透析CKD阶段3b-5和MDD在2个部位，随机1：1：1分为治疗组或对照组 临床管理组加安慰剂。我们假设，无论哪种方法还是控制方法，都会导致 抑郁症状两点改善的最小临床重要差异，如盲目确定 由抑郁症症状学快速盘点。在目标2中，我们将观察其疗效和耐受性。 8周(1)单盲BAT+安慰剂或(2)双盲安非他酮+临床治疗与 控制抑郁症状的改善。在目标3中，我们将比较这两种疗法的疗效。 改善以CKD患者为中心的结局的策略与控制，包括A.坚持药物治疗 以及就诊；B.疲劳；C.睡眠；以及D.整体功能。迫切需要临床试验来解决 慢性肾脏病患者MDD治疗存在的证据差距。确定两种不同策略的有效性 将是势在必行的，所以如果发现同样有效，最被患者接受的选择可以 在临床实践中提供。我们有在CKD成功进行多中心试验的记录 在两个地点组建了一支高素质的调查团队，以确保项目成功完成。

Project Abstract The overall goal of our research is to determine whether treatment of a Major Depressive Disorder (MDD) improves the outcomes of patients with chronic kidney disease (CKD). We showed that MDD is present in up to 25% of CKD patients and independently associated with progression of CKD to End-Stage Kidney Disease, hospitalization, and death. Depression was also shown to be associated with adverse patient-centered outcomes such as lower quality of life (QOL), fatigue, poor sleep, and non-adherence to diet and medications. However, evidence for efficacy and tolerability of commonly-used antidepressant medications or nonpharmacologic treatments are very limited in CKD patients. Previous data, primarily derived from dialysis-dependent patients, were limited by small samples, lack of randomization and control, short durations, and high dropout rates. Our group was the first to conduct a double-blind randomized controlled trial for MDD treatment in 201 patients with non-dialysis CKD, and showed that sertraline, a commonly used selective serotonin reuptake inhibitor (SSRI), was no more efficacious than placebo for improving depressive symptoms. Given the high prevalence of MDD in CKD, its association with adverse outcomes, and lack of data to support efficacy of conventional treatments, it becomes imperative to test novel strategies to treat MDD in CKD patients. We propose to compare with a control group, the efficacy and tolerability of two novel treatment strategies - (1) Behavioral Activation Teletherapy (BAT) for 16 weeks, with the addition of bupropion, a non-SSRI antidepressant, at 8 weeks for patients whose depression has not remitted (non-remitters); and (2) bupropion for 16 weeks, with the addition of BAT at 8 weeks for non-remitters. In Aim 1, we will investigate the efficacy and tolerability of these 2 strategies vs. control for improvement in a primary endpoint of depressive symptoms in 201 patients (67 per group) with non-dialysis CKD stages 3b-5 and MDD at 2 sites, randomized 1:1:1 to either strategy or a control group of Clinical Management plus placebo. We hypothesize that either approach vs. control will result in a minimal clinically important difference of 2 points improvement in depressive symptoms, as ascertained blindly by the Quick Inventory of Depressive Symptomatology. In Aim 2 we will investigate the efficacy and tolerability of 8 weeks of (1) single-blind BAT plus placebo or (2) double-blind bupropion plus Clinical Management vs. control for improvement in depressive symptoms. In Aim 3, we will compare the efficacy of these 2 treatments strategies vs. control for improvement in CKD patient-centered outcomes including a. adherence to medications and healthcare visits; b. fatigue; c. sleep; and d. overall functioning. A clinical trial is urgently needed to address the evidence gap that exists for MDD treatment in CKD patients. Establishing the efficacy of 2 different strategies would be imperative, so that if found to be comparably efficacious, the option most acceptable to patients could be offered in clinical practice. We have a track-record of successfully conducting multicenter trials in CKD and have assembled a team of highly qualified investigators at 2 sites to ensure successful project completion.