Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)

调查抑郁症对神经免疫目标影响的治疗研究 (TRIDENT)

• 批准号: 10700126
• 负责人: Adam Wayne Carrico
• 金额: --
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2023-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10700126
• 关键词: Acute; Amino Acids; Behavior Therapy; Behavioral; Brain; Catabolism; Central Nervous System; Clinical Research; Cognitive Therapy; Communication; Counseling; Depressed mood; Development; Enrollment; Epidemic; Evidence based treatment; Experimental Models; Functional Magnetic Resonance Imaging; Gastrointestinal tract structure; Gene Expression; Generations; Genetic Transcription; Goals; HIV; HIV Infections; Immune; Immune system; Immunologic Markers; Immunologics; Individual; Inflammatory; Integrase; Interoception; Leukocytes; Link; Measures; Mediator; Mental Depression; Modernization; Negative Valence; Neuroimmune; Neurosecretory Systems; Notification; Outcome; Participant; Pathogenesis; Pathway interactions; Peripheral; Persons; Pharmacological Treatment; Primary Care Physician; Psychoneuroimmunology; Psychosocial Assessment and Care; Psychosocial Factor; Randomized; Randomized, Controlled Trials; Regimen; Research; Rest; Rewards; Risk; Running; Serotonin; Signal Pathway; Signal Transduction; Subgroup; System; Tryptophan; Unipolar Depression; Up-Regulation; Vagus nerve structure; Viral Load result; Waiting Lists; acute infection; antiretroviral therapy; depressive symptoms; dysbiosis; efficacy evaluation; eligible participant; evidence base; experience; follow up assessment; gut dysbiosis; gut microbiome; gut-brain axis; improved; inhibitor; innovation; microbial; microbial products; microbiome; microbiome alteration; multidimensional data; neural; neural network; neurobehavioral; neuropsychiatric disorder; primary outcome; response; stem; therapy adherence; treatment research

Project Summary Since the early days of the epidemic, psychoneuroimmunology research established that there is a bi- directional relationship between depression and HIV pathogenesis. Among people with HIV (PWH), substantial damage to the gastrointestinal tract occurs during acute HIV infection, which is partially responsible for dysregulation of the gut microbiome (i.e., dysbiosis) and translocation of inflammatory microbial products into the periphery. Even among those receiving effective anti-retroviral therapy (ART), these pathophysiologic alterations in the gut drive persistent immune dysregulation that partially explains amplified risk for depression and other neuropsychiatric disorders in PWH. An important gap is that no prior clinical research in PWH receiving effective ART has examined the functional connections between the microbiome, gastrointestinal tract, immune system, and the brain – the microbiome-gut-brain (MGB) axis. Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT) is a randomized controlled trial that leverages an evidence-based Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) treatment as an experimental probe to advance our understanding of how decreasing depression alters MGB axis pathways in PWH. TRIDENT will enroll 120 depressed PWH taking an integrase strand transfer inhibitor (INSTI)-based ART regimen who have an undetectable viral load. TRIDENT will have a brief run-in period (i.e., waiting period prior to randomization) where potentially eligible participants will be asked to complete a baseline psychosocial assessment, provide biospecimens, and attend a separate baseline fMRI assessment. A total of 120 participants who complete the run-in period will be randomized to receive either: 1) CBT-AD (n = 60); or 2) a wait-list control (WLC) condition (n = 60). Immediately following randomization, CBT-AD participants will receive up to 12 individual sessions over 4 months. WLC participants will have the opportunity to receive the CBT-AD treatment after a 6-month delay. During the intent-to-treat period, follow-up assessments at 2 months and 4 months (i.e., during and immediately following the delivery of CBT-AD) will characterize changes in the microbiome, soluble immune markers relevant to HIV pathogenesis, and leukocyte signaling to measure the conserved transcriptional response to adversity (CTRA). These will be examined as plausible mediators of CBT-AD related improvements in the primary outcome – resting state activation and connectivity of the negative valence system at 6 months (assessed via fMRI). Six months after randomization, WLC participants will crossover and have the opportunity to receive CBT-AD, and all participants (both CBT-AD and WLC) will complete a final follow-up assessment at 10 months. TRIDENT will have an exceptional impact by providing an experimental model to advance our understanding of how decreasing depression changes the MGB axis in PWH. TRIDENT will include multi-level, high dimensional data on the MGB axis to catalyze a new generation of pharmacologic and behavioral treatments for depression and its neurobehavioral substrates in PWH.

项目摘要 自流行病早期以来，心理肌免疫学研究表明 抑郁与HIV发病机理之间的方向关系。在艾滋病毒（PWH）的人中，大量 在急性HIV感染期间，胃肠道的损害发生了部分原因，这是部分原因 肠道微生物组的失调（即营养不良）和炎症微生物产物的易位 外围。即使在接受有效抗逆转录病毒疗法（ART）的人中，这些病理生理学 肠道驱动器的改变持续的免疫失调，部分解释了放大的抑郁症风险 以及PWH中的其他神经精神疾病。一个重要的差距是，PWH没有先前的临床研究 接收有效的艺术已经检查了微生物组胃肠道之间的功能连接 区域，免疫系统和大脑 - 微生物组 - 脑（MGB）轴。治疗研究调查 抑郁对神经免疫性靶标（TRIDEN）的影响是一项随机对照试验，利用 基于证据的认知行为疗法依从性和抑郁（CBT-AD）作为一种 实验探测器以促进我们对减少抑郁症如何改变MGB轴途径的理解 PWH。 Trident将招募120个抑郁PWH服用积分酶链转移抑制剂（Insti） 具有无法检测到的病毒负荷的艺术方案。 Trident将有一个短暂的磨合期（即等待期 在随机化之前），可能会要求可能合格的参与者完成基线社会心理 评估，提供生物测量并参加单独的基线fMRI评估。总共120 完成磨合期的参与者将被随机接收：1）CBT-AD（n = 60）;或者 2）等待名单控制（WLC）条件（n = 60）。随机化后，CBT-AD参与者将 在4个月内，最多可以接受12个个人会议。 WLC参与者将有机会接收 延迟6个月后的CBT-AD处理。在意图到治疗期间，2个月的后续评估 和4个月（即，在CBT-AD交付期间和之后立即）将表征变化 微生物组，可溶性免疫标记与HIV发病机理和白细胞信号相关以测量 对广告（CTRA）的保守转录响应。这些将被检查为合理的调解人 CBT-AD主要结果的相关改进 - 静止状态激活和连通性 6个月时的负价系统（通过fMRI评估）。随机化六个月后，WLC参与者 将跨界并有机会接收CBT-AD，所有参与者（CBT-AD和WLC）都将 完成10个月的最终随访评估。三叉戟将通过提供一个特殊的影响 实验模型，以促进我们对减少抑郁症如何改变MGB轴的理解 PWH。 Trident将在MGB轴上包括多层，高维数据，以催化新一代 PWH中抑郁及其神经行为底物的药物和行为处理。