Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)

CKD 共病抑郁症的新疗法组合 (CONCORD)

基本信息

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
项目类别：
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

项目摘要

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可以治疗重度抑郁症 (MDD) 改善慢性肾脏病（CKD）患者的预后。我们发现 MDD 存在于最多 25% 的 CKD 患者与 CKD 进展为终末期肾病独立相关，住院、死亡。抑郁症也被证明与以患者为中心的不良结果相关例如生活质量 (QOL) 较低、疲劳、睡眠不佳以及不遵守饮食和药物治疗。然而，常用抗抑郁药物或非药物的疗效和耐受性的证据 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，其局限性在于样本量小、缺乏随机化和控制、持续时间短以及辍学率高。我们的该小组是第一个对 201 名 MDD 患者进行双盲随机对照试验非透析 CKD，并表明舍曲林（一种常用的选择性血清素再摄取抑制剂（SSRI）），在改善抑郁症状方面并不比安慰剂更有效。鉴于MDD的高患病率在 CKD 中，其与不良后果的关联，以及缺乏支持传统治疗疗效的数据治疗中，测试治疗 CKD 患者 MDD 的新策略变得势在必行。我们建议与对照组比较，两种新治疗策略的疗效和耐受性 - (1) 行为治疗激活远程治疗 (BAT) 16 周，并在 8 时添加安非他酮（一种非 SSRI 抗抑郁药）对于抑郁症尚未缓解的患者（非缓解者），需要数周； (2) 安非他酮 16 周，对于非汇款者，在第 8 周添加 BAT。在目标 1 中，我们将研究这 2 种药物的功效和耐受性 201 名患者（每 67 名患者）抑郁症状主要终点改善的策略与对照组）在 2 个部位进行非透析 CKD 3b-5 期和 MDD，按 1:1:1 随机分配至策略或对照临床管理加安慰剂组。我们假设任何一种方法与控制都会导致盲目确定的抑郁症状改善 2 分的临床重要差异极小通过抑郁症状学快速清单。在目标 2 中，我们将研究疗效和耐受性为期 8 周的 (1) 单盲 BAT 加安慰剂或 (2) 双盲安非他酮加临床管理 vs. 控制抑郁症状的改善。在目标 3 中，我们将比较这 2 种治疗方法的功效改善以 CKD 患者为中心的结局的策略与控制，包括：坚持用药和医疗保健就诊； b.疲劳; c.睡觉;和d。整体运作。迫切需要临床试验来解决 CKD 患者的 MDD 治疗存在证据缺口。确定两种不同策略的功效势在必行，因此，如果发现相对有效，那么最能被患者接受的选择就可以并在临床实践中提供。我们拥有成功开展 CKD 多中心试验的记录，在两个地点组建了一支高素质的调查人员团队，以确保项目成功完成。