Mechanisms for Behavior Change and Maintenance of Treatment for CKD Comorbid Depression

CKD 共病抑郁症的行为改变和维持治疗机制

• 批准号: 10667222
• 负责人: Susan Hedayati
• 金额: $ 42.6万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10667222
• 关键词: Address; Adherence; Adoption; Adverse effects; Affect; Antidepressive Agents; Behavior; Behavior Therapy; Behavioral; Behavioral Mechanisms; Biological Markers; Bupropion; Cessation of life; Chronic Kidney Failure; Clinical Management; Collection; Combination Drug Therapy; Data; Data Analyses; Dialysis procedure; Disease remission; Double-Blind Method; Equilibrium; Fatigue; Focus Groups; Freezing; Funding; Gene Expression; Gene Expression Profiling; General Population; Genomics; Hospitalization; Inflammation; Inflammation Mediators; Inflammatory; Intervention; Knowledge; Maintenance; Major Depressive Disorder; Mediating; Mental Depression; Modification; Outcome; Parents; Participant; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Plasma; Public Health; Randomized; Randomized Clinical Trials; Research Personnel; Sampling; Selective Serotonin Reuptake Inhibitor; Sertraline; Single-Blind Study; Sleep; Teletherapy; Time; TimeLine; United States National Institutes of Health; Whole Blood; Work; attentional control; behavior change; behavioral/social science; comorbid depression; comparative efficacy; depressive symptoms; experience; immune activation; improved; improved outcome; intervention effect; inventory of depressive symptomatology; nondrug therapy; novel; novel therapeutics; overtreatment; patient population; pill; predicting response; social science research; transcriptome sequencing; treatment effect; treatment response; treatment strategy; week trial

Project Summary/Abstract The purpose of this application is to understand why interventions for the treatment of Major Depressive Disorder (MDD) work or do not work initially and over time in patients with Chronic Kidney Disease (CKD). This project will add assessments to my ongoing NIH R01-funded study (R01DK124379-05), Combination of Novel Therapies for CKD Comorbid Depression, to help illuminate mechanisms of action mediating response to treatment; facilitators and barriers to adoption of treatment; and maintenance of treatment response. We will collect complimentary data that will use information from the subset of participants who have completed the parent study to investigate mechanisms for depression treatment effect, or lack thereof, and also identify the maintenance of treatment effect beyond the active intervention period in those who initially have remission in depression after 8 weeks of treatment. In the parent R01 study, we are currently comparing the efficacy of two 16-week strategies vs. control for treatment of MDD starting with (1) Behavioral Activation Therapy (BAT) or (2) bupropion drug therapy, each augmented to a combination of both in non-remitters after 8 weeks. We will engage the subset of participants that have completed the parent trial to: Aim 1. Identify mechanisms of action of intervention effect, vs. lack thereof, by identifying candidate inflammatory mediators/moderators of MDD treatment response in CKD patients. We will use (a) RNA-Sequencing of whole blood gene expression and (b) plasma inflammatory biomarkers from frozen samples that have already been collected at baseline and at week 8 from patients who completed at least 8 weeks from the parent study (N =76). We will evaluate whether there is a modification from baseline in candidate innate immune activation/inflammatory pathways through targeted whole genomic transcriptional profiling and plasma biomarkers in (a) depression remitters (defined as Quick Inventory of Depressive Symptomatology score - QIDS-SR ≤5) vs. non-remitters; and (b) responders to treatment (defined as a decrease in the QIDS-SR score by ≥3 points from baseline) vs. non-responders to treatment. Aim 2. Assess underlying facilitators of or barriers to behavior adoption, in this case adherence to MDD treatment interventions (drug by pill count and BAT teletherapy sessions), in patients with CKD. We will conduct focus groups in 50 participants who have finished the 16-week trial to gather data on participants’ experiences, barriers to and facilitators of intervention engagement and adherence, and perceived benefits of the intervention. Aim 3. Assess maintenance of MDD treatment response over time, beyond the 16-week active intervention period (N =50), in remitters vs. non-remitters at 8 weeks, by assessing improvement in patient-centered outcomes of (a) depressive symptoms; (b) fatigue; (c) sleep; (d) overall functioning. This application corresponds with my parent R01’s scope and timeline and the purpose and requirements of the Office of Behavioral and Social Sciences Research. The aims will not interfere and do not overlap with the original scope of the parent R01.

项目概要/摘要 此应用程序的目的是了解为什么要采用干预措施来治疗重度抑郁症 慢性肾脏病 (CKD) 患者的疾病 (MDD) 最初或随着时间的推移不起作用。 项目将为我正在进行的 NIH R01 资助的研究 (R01DK124379-05) 添加评估，小说的组合 慢性肾病共病抑郁症的治疗，有助于阐明介导反应的作用机制 治疗；采用治疗的促进因素和障碍；以及治疗反应的维持。 收集补充数据，这些数据将使用来自已完成该任务的子集的信息 家长研究旨在调查抑郁症治疗效果或缺乏效果的机制，并确定 在最初缓解的患者中，在积极干预期之后维持治疗效果 在母体 R01 研究中，我们目前正在比较两种药物治疗 8 周后的疗效。 MDD 治疗的 16 周策略与对照从 (1) 行为激活疗法 (BAT) 或 (2) 开始 安非他酮药物治疗，8 周后，非缓解者将每种药物联合治疗。 让已完成家长试验的参与者子集参与进来： 目标 1. 确定机制 通过识别候选炎症来比较干预效果的作用与缺乏干预效果 CKD 患者 MDD 治疗反应的调节因子/调节因子 我们将使用 (a) 整体 RNA 测序。 血液基因表达和（b）来自已冷冻样本的血浆炎症生物标志物 在基线和第 8 周从完成母研究至少 8 周的患者中收集 (N =76）。我们将评估候选先天免疫是否较基线发生改变。 通过靶向全基因组转录谱和血浆激活/炎症途径 (a) 抑郁症缓解者中的生物标志物（定义为抑郁症状快速清单评分 - QIDS-SR ≤5) 与非缓解者；和 (b) 对治疗有反应的人（定义为 QIDS-SR 评分下降） 与对治疗无反应者相比，增加 ≥3 分 目标 2. 评估潜在的促进因素或治疗因素。 采取行为的障碍，在这种情况下，坚持 MDD 治疗干预措施（按药丸计数） 和 BAT 远程治疗课程），我们将对 50 名患有 CKD 的患者进行焦点小组讨论。 完成了为期 16 周的试验，收集有关参与者的经历、干预的障碍和促进因素的数据 目标 3. 评估 MDD 的维持情况。 超过 16 周积极干预期 (N = 50) 后，缓解者与对照组的治疗反应随时间变化 通过评估 (a) 抑郁症以患者为中心的结果的改善，在 8 周时未缓解 症状；(b) 疲劳；(d) 整体功能。 行为和社会科学办公室的范围和时间表以及目的和要求 研究目标不会干扰母版 R01 的原始范围，也不会重叠。