Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)

CKD 共病抑郁症的新疗法组合 (CONCORD)

• 批准号: 10640205
• 负责人: Susan Hedayati
• 金额: $ 69万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2023-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10640205
• 关键词: Address; Adherence; Affect; Antidepressive Agents; Behavior Therapy; Behavioral; Bupropion; C-reactive protein; Cessation of life; Chronic Kidney Failure; Clinic; Clinical; Clinical Management; Clinical Trials; Cognitive; Cognitive Therapy; Combination Drug Therapy; Combined Modality Therapy; Control Groups; Data; Dialysis procedure; Diet; Disease remission; Double-Blind Method; Dropout; End stage renal failure; Ensure; Equipoise; Fatigue; General Population; Goals; Health Care Visit; Health Services Accessibility; High Prevalence; Hospitalization; Improve Access; Internet; Intervention; Major Depressive Disorder; Mental Depression; Multicenter Trials; Patient Preferences; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Plasma; Public Health; Qualifying; Quality of life; Randomized; Randomized, Controlled Trials; Research; Research Personnel; Sampling; Sedation procedure; Selective Serotonin Reuptake Inhibitor; Sertraline; Single-Blind Study; Site; Sleep; Teletherapy; Testing; Travel; Treatment Efficacy; adverse outcome; arm; attentional control; clinical practice; comorbid depression; comparative efficacy; conventional therapy; depressive symptoms; efficacious treatment; gastrointestinal; improved; improved outcome; inventory of depressive symptomatology; nondrug therapy; novel; novel strategies; novel therapeutics; poor sleep; primary endpoint; randomized trial; treatment strategy

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.

项目摘要 我们研究的总体目标是确定是否治疗重大抑郁症（MDD） 改善慢性肾脏疾病（CKD）患者的结局。我们证明MDD存在于 25％的CKD患者，与CKD发展到终末期肾脏疾病的独立相关， 住院和死亡。抑郁症也被证明与以患者为中心的不利结局有关 例如较低的生活质量（QOL），疲劳，睡眠不佳以及对饮食和药物的不遵守。然而， 常用抗抑郁药或非药物的功效和耐受性的证据 CKD患者的治疗非常有限。以前的数据主要来自透析依赖性患者， 受小样本的限制，缺乏随机和对照，持续时间短，辍学率很高。我们的 组是第一个在201个患者中进行MDD治疗双盲随机对照试验的人 非透析CKD，并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比安慰剂更有效。鉴于MDD的高患病率 在CKD中，它与不良结果的关联以及缺乏支持常规功效的数据 治疗方法，必须测试在CKD患者中治疗MDD的新型策略。我们建议 与对照组，两种新型治疗策略的功效和耐受性进行比较 - （1）行为 激活远程疗法（BAT）持续16周，加上安非他酮，一种非SSRI抗抑郁药，在8 抑郁症的患者几周（非临床者）； （2）安非他酮16周， 在8周内为非射击者增加蝙蝠。在AIM 1中，我们将研究这2 201例患者的抑郁症状的主要终点的策略与控制改善（每人67 组）在2个站点上具有非透析CKD阶段3B-5阶段，MDD随机1：1：1以策略或对照 一组临床管理加安慰剂。我们假设两种方法与控制都将导致 由于盲目确定 通过抑郁症状的快速清单。在AIM 2中，我们将研究功效和耐受性 8周的（1）单盲蝙蝠加安慰剂或（2）双盲安非他酮加上临床管理VS。 控制抑郁症状的改善。在AIM 3中，我们将比较这两种治疗的功效 策略与控制CKD以患者为中心的结果的控制，包括a。遵守药物 和医疗访问； b。疲劳; c。睡觉;和d。总体功能。迫切需要进行临床试验来解决 CKD患者中MDD治疗存在的证据差距。建立两种不同策略的功效 必须是必须的 在临床实践中提供。我们拥有成功在CKD中成功进行多中心试验的轨道记录和 已经在两个站点组成了一支高素质的调查员团队，以确保成功完成项目。