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 从流行病的早期开始，心理神经免疫学研究就证实， 抑郁症与艾滋病发病的直接关系。在艾滋病毒感染者中， 在急性HIV感染期间发生胃肠道损伤，这是导致 肠道微生物组的失调（即，微生态失调）和炎性微生物产物易位到 外围。即使在那些接受有效的抗逆转录病毒治疗（ART），这些病理生理 肠道的改变驱动持续的免疫失调，部分解释了抑郁症风险的放大 和其他神经精神疾病。一个重要的差距是，之前没有关于PWH的临床研究， 接受有效的ART检查了微生物组，胃肠道和肠道之间的功能联系。 肠道，免疫系统和大脑-微生物组-肠道-大脑（MGB）轴。治疗研究调查 抑郁对神经免疫靶点的影响（TRIDENT）是一项随机对照试验， 循证认知行为治疗依从性和抑郁症（CBT-AD）治疗作为一种 实验探索，以促进我们对减少抑郁症如何改变MGB轴通路的理解， PWH。TRIDENT将招募120名抑郁症PWH患者，他们服用基于整合酶链转移抑制剂（INFl）的药物。 ART方案的患者，病毒载量检测不到。TRIDENT将有一个短暂的磨合期（即，等待期 随机化前），其中将要求潜在合格的受试者完成基线心理社会学评估。 评估，提供生物标本，并参加单独的基线fMRI评估。共120 完成导入期的参与者将随机接受：1）CBT-AD（n = 60）;或 2)等待列表控制（WLC）条件（n = 60）。随机化后，CBT-AD受试者将立即 在4个月内接受多达12次单独治疗。WLC参与者将有机会获得 CBT-AD治疗延迟6个月后。在意向治疗期间，2个月时的随访评估 和4个月（即，在交付CBT-AD期间和之后立即）将表征 微生物组、与HIV发病机制相关的可溶性免疫标志物和白细胞信号传导，以测量 逆境保守转录反应（CTRA）。这些将被检查作为合理的调解人， CBT-AD相关的主要结局改善-静息状态激活和连接 6个月时的负效价系统（通过fMRI评估）。随机化后6个月，WLC参与者 将交叉，并有机会获得CBT-AD，所有参与者（CBT-AD和WLC）将 在10个月时完成最终随访评估。TRIDENT将通过提供 实验模型，以促进我们的理解如何减少抑郁症改变MGB轴， PWH。TRIDENT将包括MGB轴上的多层次、高维数据，以催化新一代 药物和行为治疗的抑郁症及其神经行为基板在PWH。