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RCT Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (Rest)

通过曲唑酮（休息）改善睡眠来针对早期阿尔茨海默病认知的随机对照试验

基本信息

批准号：
10180391
负责人：
Barry David Greenberg
金额：
$ 78.56万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10180391
关键词：
Acute Affect Alleles Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer’s disease biomarker Amyloid Amyloid deposition Animal Model Animals Antidepressive Agents Attention Benign Biological Markers Brain Cerebrospinal Fluid Cognition Cognitive Cross-Over Trials Data Dementia Development Disease Disease Progression Double-Blind Method Drug Targeting Elderly FDA approved Family Caregiver Functional Magnetic Resonance Imaging Health Care Costs Hippocampus (Brain)Home Human Impaired cognition Impairment Individual Insecta Intercellular Fluid Link Measures Mediating Memory Modification Morbidity - disease rate Observational Study Outcome Pathogenesis Pathogenicity Pathologic Pathology Pathway interactions Patient Self-Report Pattern Performance Persons Pharmaceutical Preparations Phase Placebos Polysomnography Process Public Health Quality of life Randomized Research Personnel Rest Risk Rodent Safety Sleep Sleep Deprivation Sleep Fragmentations Sleep disturbances Slow-Wave Sleep Study models Surrogate Markers Testing Therapeutic Time Trazodone Wakefulness actigraphy amnestic mild cognitive impairment apolipoprotein E-4 base blood-based biomarker cognitive performance cognitive task cost disability effective therapy executive function follow-up glymphatic system hemodynamics improved informant interstitial magnetic resonance imaging biomarker mild cognitive impairment neuropsychiatric symptom off-label use phase III trial poor sleep prevent primary outcome processing speed prodromal Alzheimer&apos s disease relating to nervous system response secondary outcome side effect sleep onset symptom treatment tau Proteins tau-1 therapy development trial comparing vigilance

项目摘要

PROJECT SUMMARY It is estimated that 5.8 million people are afflicted by dementia in the US, a number projected to increase to 14 million by 2050 unless effective therapies are available that prevent or significantly slow the disease process. Sleep complaints are common throughout the AD continuum beginning with prodromal stages. In observational studies, disturbed sleep has been linked to AD pathogenesis and subsequent development of mild cognitive impairment (MCI) and dementia. Co-investigator Dr. Bakker has studied pattern separation (PS; a memory task involved with the earliest stages of encoding that is essential to formation of new memories) in a task related functional MRI (fMRI) paradigm, determining that impaired PS is associated with increased hippocampal activation in amnestic MCI (aMCI). Because poor sleep may be associated with increased hippocampal activation, improving sleep is a potential target for positively affecting cognition and disease progression in AD. Trazodone is a generic antidepressant widely used off-label to treat sleep disturbance, particularly enhancing slow wave sleep (SWS) that is evidenced to be a critical sleep phase influencing pathogenic mechanisms. While it has been demonstrated to improve sleep in AD and potentially mitigate the risk of developing MCI, its effect on sleep has not been rigorously studied in MCI. Supported by its benign safety profile, we propose a rigorous double-blind, placebo-controlled, randomized crossover trial of trazodone in 100 subjects with prodromal AD/aMCI and sleep complaints. Each treatment phase will last four weeks with a two-week washout between phases. Sleep will be measured by home sleep testing including polysomnography, actigraphy, and self-report. Hippocampal function and excitability will be assessed by task-related fMRI employing PS. The primary outcome will be to examine the association of trazodone with sleep parameters. We hypothesize that trazodone will improve total sleep time and proportion of time in SWS. Secondary outcomes include assessment of trazodone's effect on 1) PS and hippocampal activation by task-related fMRI, with the hypothesis that trazodone will improve PS performance and decrease hippocampal activation; 2) a broader range of cognitive domains, with the hypothesis that trazodone will improve performance on other memory tasks, executive function, and processing speed; 3) neuropsychiatric symptoms with the hypothesis that they will improve with trazodone treatment. We will also assess blood- based biomarkers of amyloid and tau, as exploratory outcomes to assess their association with sleep and cognitive responses to trazodone.

项目总结