Brain Amyloid- Retention During Wakefulness and Following Emergence From Sleep in Healthy People

NCT02669225 | Completed Early Phase 1

• 2 other identifiers: 16005916-AA-0059
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Normal Physiology

Keywords

[18F]florbetaben; Sleep Deprivation; rested wakefulness; glymphatic system

Outcome Measures

Primary Outcomes (2)

• (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.

  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.

  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...

  end of study

Study Arms (2)

Rested Wakefulness

EXPERIMENTAL

RW PET/MR Scanning Sessions

Other: [18F]florbetaben

Sleep Deprivation

EXPERIMENTAL

SD PET/MR Scanning Sessions

Other: [18F]florbetaben

Interventions

[18F]florbetaben OTHER

PET radiotracer to image Amyloid beta (AB) load in human brain.

Rested Wakefulness; Sleep Deprivation

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or females.
• Young group (18-40 years of age)
• Older group (\>40 years of age)
• Ability to provide written informed consent

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sleep Deprivation

Interventions

4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Condition Hierarchy (Ancestors)

Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Officials

• Dardo G Tomasi, Ph.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2016
• First Posted: February 1, 2016
• Study Start: May 2, 2016
• Primary Completion: January 24, 2017
• Study Completion: July 11, 2018
• Last Updated: April 20, 2026

Record last verified: 2025-10-22

Locations

US (1)