Orexin and Tau Pathology in Cognitively Normal Elderly
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|ClinicalTrials.gov Identifier: NCT03053908|
Recruitment Status : Completed
First Posted : February 15, 2017
Last Update Posted : February 24, 2021
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles. Current consensus is that the AD pathological process begins decades before clinical symptoms occur. This long "preclinical" phase of AD might first become detectable in middle-age as deposits of hyperphosphorylated tau (P-tau) in the transentorhinal cortex and subcortical nuclei such as the locus coeruleus (LC) and the nucleus basalis of Meynert. There is strong preliminary evidence showing that cerebrospinal fluid (CSF) levels of orexin-A (OxA) are associated with increased P-tau (r=.52, p<.01) and total-tau (T-tau) (r=.42, p<.01) in cognitively normal older adults (mean age: 69.6±8.6 years).
This study poses that onset of tauopathy in the LC results in down regulation of orexin receptors, leading to a homeostatic increase of OxA production by the hypothalamus, which results in changes in core body temperature (CBT) and sleep disruption that cause further neurodegeneration. This hypothesis will be tested by demonstrating that increases in CSF P-tau are associated in vivo with tau PET uptake, and that tau binding in the LC is associated with increases in CSF OxA (Aim 1); and second, by analyzing the downstream consequences of increased central nervous system (CNS) OxA on sleep architecture and CBT (Aim 2). To test these hypotheses, 19 older adults (age 55-75) balanced by sex, will first perform a full clinical evaluation and PET-MRI where Tau burden will be analyzed by PET-MR using 18F-MK6240 (visits 1-2). Subjects will later undergo 7 days of actigraphy followed by nocturnal polysomnography (NPSG) for 2 consecutive nights (N1-2) during which we will measure CBT (visits 3-4). A morning lumbar puncture (LP) will be performed after N2 to obtain CSF.
|Condition or disease||Intervention/treatment||Phase|
|Elderly Alzheimer Disease||Procedure: Actigraphy Procedure: Nocturnal Polysomnograpahy (NPSG)||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Orexin and Tau Pathology in Cognitively Normal Elderly (A New Prevention Strategy for Alzheimer's Disease)|
|Actual Study Start Date :||March 27, 2018|
|Actual Primary Completion Date :||May 13, 2019|
|Actual Study Completion Date :||May 13, 2019|
|Experimental: Elderly Patients||
Recording of sleep/wake cycle and TST by actigraphy to be completed at home by subject over 7 days
Procedure: Nocturnal Polysomnograpahy (NPSG)
N1 habituation and N2 data collection
- Cerebral Spinal Fluid (CSF) P-Tau measured with PET-MR [ Time Frame: 4 Weeks ]CSF P-tau is associated with cortical tau uptake
- 18MK6240 binding amount measured with PET-MR [ Time Frame: 2 weeks ]Tau binding in the brainstem is associated with increases in CSF OxA. PET-MR using 18MK6240 (PET Radiotracer for Imaging Neurofibrillary), which will be performed 1-4 weeks before the LP (visit 2).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03053908
|United States, New York|
|New York University School of Medicine|
|New York, New York, United States, 10016|
|Principal Investigator:||Ricardo Osorio, M.D||NYU Langone Health|