Ignite Creation Date:
2024-05-06 @ 8:05 AM
Last Modification Date:
2024-10-26 @ 11:56 AM
Study NCT ID:
NCT02669225
Status:
COMPLETED
Last Update Posted:
2024-06-10
First Post:
2016-01-29
Brief Title:
Brain Amyloid- Retention During Wakefulness and Following Emergence From Sleep in Healthy People
Sponsor:
National Institute on Alcohol Abuse and Alcoholism NIAAA
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Characterization of Brain Amyloid-beta A-beta Retention During Wakefulness And Following Emergence From Sleep In Healthy Subjects
Status:
COMPLETED
Status Verified Date:
2023-12-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Brain activity creates waste products The body s glymphatic system removes this waste especially during sleep One brain waste product is amyloid-beta Ab It plays a role in Alzheimer s disease Researchers want to study the effect of sleep on Ab in the brain
Objective
To see if sleep affects the amount of waste product removed from the brain
Eligibility
Healthy people at least 18 years of age
Design
Participants will be screened with a medical history physical exam and blood and urine tests They will answer questions about drug use psychiatric history and family history of alcoholism or drug use Participants will complete an MRI screening questionnaire
Participants will stay in the clinic overnight two times On one night they will sleep through the night On the other night they will be kept awake all night These overnight visits can happen in any order
Participants will wear 2 activity monitors on the wrist and the ankle
Participants will have positron emission tomography PET scans A small amount of a radioactive chemical will be injected through an intravenous IV catheter Participants will lie on a bed that slides into the scanner A cap or a special mask may be placed on the participant s head
Participants will have magnetic resonance imaging MRI scans The MRI scanner is a metal cylinder in a strong magnetic field Participants will lie on a table that slides into the cylinder A device called a coil will be placed over the head Participants will do a task on a computer screen in the scanner
Participants will have tests of thinking memory and attention They may be interviewed complete questionnaires take pen-and-paper or computer tests and perform simple actions
Brain activity creates waste products The body s glymphatic system removes this waste especially during sleep One brain waste product is amyloid-beta Ab It plays a role in Alzheimer s disease Researchers want to study the effect of sleep on Ab in the brain
Objective
To see if sleep affects the amount of waste product removed from the brain
Eligibility
Healthy people at least 18 years of age
Design
Participants will be screened with a medical history physical exam and blood and urine tests They will answer questions about drug use psychiatric history and family history of alcoholism or drug use Participants will complete an MRI screening questionnaire
Participants will stay in the clinic overnight two times On one night they will sleep through the night On the other night they will be kept awake all night These overnight visits can happen in any order
Participants will wear 2 activity monitors on the wrist and the ankle
Participants will have positron emission tomography PET scans A small amount of a radioactive chemical will be injected through an intravenous IV catheter Participants will lie on a bed that slides into the scanner A cap or a special mask may be placed on the participant s head
Participants will have magnetic resonance imaging MRI scans The MRI scanner is a metal cylinder in a strong magnetic field Participants will lie on a table that slides into the cylinder A device called a coil will be placed over the head Participants will do a task on a computer screen in the scanner
Participants will have tests of thinking memory and attention They may be interviewed complete questionnaires take pen-and-paper or computer tests and perform simple actions
Detailed Description:
Objective
To assess if there are differences in 18Fflorbetaben uptake following the first 120 minutes of its injection reflecting amyloid-beta or Ab load andor docked Ab in subjects during rested wakefulness RW after normal sleep compared to wakefulness after 24 hrs of sleep deprivation SD Specifically we hypothesize that during RW after a normal night s sleep there will be less 18Fflorbetaben binding measured as distribution volume ratios DVR in precuneus relative to cerebellum reflecting normal brain clearing of Ab overnight when compared to wakefulness after SD which would interfere with Ab removal from the brain s interstitial space Though we will be measuring Ab in whole brain our analysis will focus in precuneus since this is the brain region that shows the higher levels of Ab accumulation in contrast to cerebellum where there is no accumulation of Ab Therefore overall Ab load in precuneus as reflected by 18Fflorbetaben DVR will be lower during RW compared to SD MRI and 1H-MRS will be used secondarily to assess if there are differences in connectivity function and neurochemistry in precuneus between RW and SD Because the rate of CSF production as well as Ab clearance from CSF differs as a function of age the current study will also allow us to assess if the higher Ab brain levels reported in older than in younger individuals reflect greater Ab clearance in younger than older individuals
Study population
Two groups consisting of healthy young adults 18 - 40 years of age and healthy older adults 40 years of age Males and females will be included
Design
Observational study We will complete testing in 15 healthy controls in each group for a total of thirty subjects n30 to assess the brain uptake of 18Fflorbetaben scan done for 120 minutes following tracer injection The order of the scans RW vs SD will be randomized MRI scans will be obtained either before or after the PET scanning session done following 18Fflorbetaben injection
Outcome measures
Uptake of 18Fflorbetaben in the brain will be measured after RW and after SD Primary outcomes will be differences in uptake and clearance of 18Fflorbetaben in precuneus reflecting A beta load andor docked A beta in subjects after SD compared to after RW as measured with distribution volume ratios using cerebellum as reference region and that clearance of Ab brain difference between RW and SD will be greater in younger than in older participants We hypothesize that Ab load in precuneus 18Fflorbetaben DVR will be higher after SD than RW and that this difference will be larger for younger than older participants We also predict that older individuals will have higher brain accumulation of Ab than younger ones In addition we will assess differences in mean water diffusivity in brain lactate concentration functional connectivity at rest and functional activation during an attention task between RW and SD conditions We predict lower fMRI signals in dorsal attention network DAN during attention task lower functional connectivity in the default mode network DMN and lower functional connectivity and mean diffusivity for SD than for RW We further predict higher concentration of lactate a marker of anaerobic metabolism for SD than for RW As exploratory analysis we will also assess based on the scans obtained after RW if individuals with higher brain Ab accumulation will have worse cognitive performance on neuropsychological tests than those with low brain Ab
To assess if there are differences in 18Fflorbetaben uptake following the first 120 minutes of its injection reflecting amyloid-beta or Ab load andor docked Ab in subjects during rested wakefulness RW after normal sleep compared to wakefulness after 24 hrs of sleep deprivation SD Specifically we hypothesize that during RW after a normal night s sleep there will be less 18Fflorbetaben binding measured as distribution volume ratios DVR in precuneus relative to cerebellum reflecting normal brain clearing of Ab overnight when compared to wakefulness after SD which would interfere with Ab removal from the brain s interstitial space Though we will be measuring Ab in whole brain our analysis will focus in precuneus since this is the brain region that shows the higher levels of Ab accumulation in contrast to cerebellum where there is no accumulation of Ab Therefore overall Ab load in precuneus as reflected by 18Fflorbetaben DVR will be lower during RW compared to SD MRI and 1H-MRS will be used secondarily to assess if there are differences in connectivity function and neurochemistry in precuneus between RW and SD Because the rate of CSF production as well as Ab clearance from CSF differs as a function of age the current study will also allow us to assess if the higher Ab brain levels reported in older than in younger individuals reflect greater Ab clearance in younger than older individuals
Study population
Two groups consisting of healthy young adults 18 - 40 years of age and healthy older adults 40 years of age Males and females will be included
Design
Observational study We will complete testing in 15 healthy controls in each group for a total of thirty subjects n30 to assess the brain uptake of 18Fflorbetaben scan done for 120 minutes following tracer injection The order of the scans RW vs SD will be randomized MRI scans will be obtained either before or after the PET scanning session done following 18Fflorbetaben injection
Outcome measures
Uptake of 18Fflorbetaben in the brain will be measured after RW and after SD Primary outcomes will be differences in uptake and clearance of 18Fflorbetaben in precuneus reflecting A beta load andor docked A beta in subjects after SD compared to after RW as measured with distribution volume ratios using cerebellum as reference region and that clearance of Ab brain difference between RW and SD will be greater in younger than in older participants We hypothesize that Ab load in precuneus 18Fflorbetaben DVR will be higher after SD than RW and that this difference will be larger for younger than older participants We also predict that older individuals will have higher brain accumulation of Ab than younger ones In addition we will assess differences in mean water diffusivity in brain lactate concentration functional connectivity at rest and functional activation during an attention task between RW and SD conditions We predict lower fMRI signals in dorsal attention network DAN during attention task lower functional connectivity in the default mode network DMN and lower functional connectivity and mean diffusivity for SD than for RW We further predict higher concentration of lactate a marker of anaerobic metabolism for SD than for RW As exploratory analysis we will also assess based on the scans obtained after RW if individuals with higher brain Ab accumulation will have worse cognitive performance on neuropsychological tests than those with low brain Ab
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 16-AA-0059 | None | None | None |