Normal PhysiologyEarly Phase 1NCT02669225
Brain Amyloid- Retention During Wakefulness and Following Emergence From Sleep in Healthy People
A Early Phase 1 study testing [18F]florbetaben in people with Normal Physiology, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Normal Physiology
- What is being tested?
- [18F]florbetaben
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 2 May 2016to 11 Jul 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or females.
- Young group (18-40 years of age)
- Older group (>40 years of age)
- Ability to provide written informed consent
Who cannot join
- Pregnant and/or breast feeding. Females of childbearing potential must have negative urine pregnancy test and not be currently breastfeeding. Post-menopausal or surgically sterile (tubal ligation or hysterectomy) females satisfy these criteria.
- Positive urine drug test for controlled substances (cocaine, methamphetamine, amphetamines, opioids, cannabinoids, benzodiazepines and barbiturates) on each visit involving imaging studies and/or neuropsychological assessment.
- Head trauma with loss of consciousness for more than 30 minutes as determined by self-report and/or medical history.
- Subjects with problematic insomnia as determined by self-report (reports having trouble sleeping on most days).
- Subjects with any of the following: narcolepsy, obstructive sleep apnea (OSA) and/or abnormal sleeping patterns (including but not limited to those who use a CPAP machine, sleeping during the day, using medication to fall asleep, sleeps less than 5 hours per night, night shift workers) as determined by self-report and/or medical history.
- Use, in the past two weeks, of psychoactive medications (four weeks for fluoxetine) or medications that may affect brain function (including but not limited to opioid analgesics, antidepressants, antipsychotics, benzodiazepines and barbiturates, stimulants) as determined by self-report and/or medical history.
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- Current DSM 5 diagnosis of affective disorder, addiction (other than nicotine of caffeine), PTSD, or schizophrenia.
- Individuals with cognitive impairment as identified with a score of lower than 24 in the MMSE will be excluded. Further, individuals with impairment sufficient to affect consent capacity even if MMSE is less than 24 will be excluded. We will consult the Ability to Consent Assessment Team (ACAT) in those whose capacity to consent may be questionable.
- Severe medical problems that can permanently impact brain function (e.g., problems of the CNS; cardiovascular; metabolic, autoimmune, endocrine) as determined by history and clinical exam.
- Individuals with a medical history of a neurodegenerative disease.
- Heavy alcohol users. Heavy alcohol users are those individuals who consume more than 5 drinks in one seating (if males) or more than 4 drinks in one seating (if females) more than twice a week will be excluded.
- Uncontrolled hypertension.
- Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces as determined by the self-report checklist.
- Fear of enclosed spaces (claustrophobia) as determined by self-report and medical history.
- Cannot lie comfortably flat on the back for up to 2 hours in the MRI scanner as determined by self-report.
- Body weight > 250 kg. This is the upper limit that the bed of the MR scanner can accommodate (clinical exam).
- Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam.
- Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Characterization of Brain Amyloid-beta (A-beta) Retention During Wakefulness And Following Emergence From Sleep In Healthy Subjects
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.
Read more
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.
Read the detailed description
Objective:
To assess if there are differences in [18F]florbetaben uptake following the first 120 minutes of its injection (reflecting amyloid-beta or Ab load and/or 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 [18F]florbetaben 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 [18F]florbetaben 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 (n=30) to assess the brain uptake of [18F]florbetaben (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 [18F]florbetaben injection.
Outcome measures:
Uptake of [18F]florbetaben in the brain will be measured after RW and after SD. Primary outcomes will be differences in uptake and clearance of [18F]florbetaben in precuneus (reflecting A beta load and/or 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 [18F]florbetaben 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.
- Conditions
- Normal Physiology
- Being tested
- [18F]florbetaben
- Keywords
- [18F]florbetaben, Sleep Deprivation, rested wakefulness, glymphatic system
- Medical subject headings
- Sleep Deprivation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]florbetabenOther
PET radiotracer to image Amyloid beta (AB) load in human brain.
| Study group | Role | What they receive |
|---|---|---|
| Rested Wakefulness | Experimental | RW PET/MR Scanning Sessions Receives: Other: [18F]florbetaben |
| Sleep Deprivation | Experimental | SD PET/MR Scanning Sessions Receives: Other: [18F]florbetaben |
What is being measured
The primary outcome is the main question the study is designed to answer.
(1) To assess if there are differences in [18F] florbetaben binding(reflecting A load) in subjects after SD compared to RW when measured in the morning.
We hypothesize that after SD there will be less clearance of A compared to RW. Therefore, overall brain A load (as reflected by [18F] florbetaben DVRs) will be higher after SD compared to RW.
Measured: end of study
(2) To assess if there are differences in brain A accumulation during RW and SD and to assess if there are differences in brain Aclearance (comparisons of RW versus SD) between young and older participants.
We hypothesize that A brain accumulation will be higher in older than younger participants both during RW and SD and that the differences in brain A (Cross)between RW and SD would be greater in younger than older participants due to greater clearance during SD.
Measured: end of study
Secondary outcomes (1)
This is an exploratory aim to assess if there are differences in brain function and neurochemistry between RW and SD using MRI and 1H-MRS and determine if the variability on the effects of SD is related to differences in brain glymphatic functio...
We hypothesize lower fMRI signals in DAN during a visual attention task, lower functional connectivity in DMN, and lower mean diffusivity in ventral precuneus for SD than for RW. We further hypothesize that higher concentration of lactate, a marker of anaerobic metabolism, on 1H-MRS for SD than for RW. We also hypothesize that brain accumulation (particularly during RW) will be associated with worse cognitive performance on neuropsychological tests.
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2016 (estimated)
- Study start2 May 2016
- Primary completion24 Jan 2017
- Study completion11 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Dardo G Tomasi, Ph.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02669225
- Sponsor's protocol ID
- 160059
- Other IDs
- 16-AA-0059
- Status last verified
- 10 Sep 2026
- First submitted
- 29 Jan 2016
- Last updated
- 14 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Brain Amyloid-beta (A-beta) Retention During Wakefulness And Following Emergence From Sleep In Healthy Subjects
- ClinicalTrials.gov ID
- NCT02669225
- Acronym / sponsor ID
- 160059
- Conditions
- Normal Physiology
- Keywords
- [18F]florbetaben, Sleep Deprivation, rested wakefulness, glymphatic system
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 2 May 2016 (actual)
- Primary completion
- 24 Jan 2017 (actual)
- Study completion
- 11 Jul 2018 (actual)
- First posted
- 1 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objective:
To assess if there are differences in [18F]florbetaben uptake following the first 120 minutes of its injection (reflecting amyloid-beta or Ab load and/or 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 [18F]florbetaben 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 [18F]florbetaben 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 (n=30) to assess the brain uptake of [18F]florbetaben (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 [18F]florbetaben injection.
Outcome measures:
Uptake of [18F]florbetaben in the brain will be measured after RW and after SD. Primary outcomes will be differences in uptake and clearance of [18F]florbetaben in precuneus (reflecting A beta load and/or 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 [18F]florbetaben 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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rested Wakefulness | Experimental | Other: [18F]florbetabenRW PET/MR Scanning Sessions |
| Sleep Deprivation | Experimental | Other: [18F]florbetabenSD PET/MR Scanning Sessions |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
Key exclusion criteria (18 listed)
- Pregnant and/or breast feeding. Females of childbearing potential must have negative urine pregnancy test and not be currently breastfeeding. Post-menopausal or surgically sterile (tubal ligation or hysterectomy) females satisfy these criteria.
- Positive urine drug test for controlled substances (cocaine, methamphetamine, amphetamines, opioids, cannabinoids, benzodiazepines and barbiturates) on each visit involving imaging studies and/or neuropsychological assessment.
- Head trauma with loss of consciousness for more than 30 minutes as determined by self-report and/or medical history.
- Subjects with problematic insomnia as determined by self-report (reports having trouble sleeping on most days).
- Subjects with any of the following: narcolepsy, obstructive sleep apnea (OSA) and/or abnormal sleeping patterns (including but not limited to those who use a CPAP machine, sleeping during the day, using medication to fall asleep, sleeps less than 5 hours per night, night shift workers) as determined by self-report and/or medical history.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]florbetabenPET radiotracer to image Amyloid beta (AB) load in human brain. | Other | Rested Wakefulness, Sleep Deprivation |
Primary outcome
(1) To assess if there are differences in [18F] florbetaben binding(reflecting A load) in subjects after SD compared to RW when measured in the morning.
Time frame: end of study
We hypothesize that after SD there will be less clearance of A compared to RW. Therefore, overall brain A load (as reflected by [18F] florbetaben DVRs) will be higher after SD compared to RW.
(2) To assess if there are differences in brain A accumulation during RW and SD and to assess if there are differences in brain Aclearance (comparisons of RW versus SD) between young and older participants.
Time frame: end of study
We hypothesize that A brain accumulation will be higher in older than younger participants both during RW and SD and that the differences in brain A (Cross)between RW and SD would be greater in younger than older participants due to greater clearance during SD.
1 secondary outcome
This is an exploratory aim to assess if there are differences in brain function and neurochemistry between RW and SD using MRI and 1H-MRS and determine if the variability on the effects of SD is related to differences in brain glymphatic functio...
Time frame: end of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dardo G Tomasi, Ph.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [18F]florbetaben in people with Normal Physiology, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
(1) To assess if there are differences in [18F] florbetaben binding(reflecting A load) in subjects after SD compared to RW when measured in the morning. (time frame: end of study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.