Human Brain Mapping of the Apparent Diffusion Coefficient (ADC) During Sleep and Wakefulness

NCT02311374 | Completed Early Phase 1

• 2 other identifiers: 15003115-AA-0031
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- The glymphatic system helps keep harmful waste from building up in the brain. Researchers think it is more active in people during sleep than while awake. They want to study the glymphatic system using magnetic resonance imaging (MRI). Objective: \- To see if there are differences in the way waste is removed from the brain while a person is sleeping versus awake. Eligibility: \- Healthy people age 18-60. Design:

• This study is in 2 parts.
• For the technical part (discontinued), participants will be screened with medical history and physical exam. They will have urine and breath alcohol tests.
• Participants will have 2 MRI scans. Before the scans, they will have urine and breath alcohol tests, and complete a questionnaire.
• For MRI, participants will lie on a table that slides in and out of a metal cylinder. A device will be placed over their head. They will lie still for up to 20 minutes at a time. They may be asked to stay awake or fall asleep for up to 2 hours at a time.
• For the research part, participants will be screened with medical history and physical exam. They will have urine and breath alcohol tests. For 1 week they will wear a device that monitors their activity and sleep.
• Participants will stay at NIH overnight. They will give a blood sample, have urine and breath alcohol tests, and complete a questionnaire.
• Participants will take memory, concentration, and thinking tests.
• Participants will have 3 MRI scans. An electroencephalography machine will record their brain activity. Electrodes will be placed on their scalp.

Conditions

Brain Mapping

Keywords

Human Brain; Sleep; EEG; Magnetic Resonance Imaging (MRI); Apparent Diffusion Coefficient (ADC)

Outcome Measures

Primary Outcomes (1)

• To assess if there is an increase in the apparent diffusion coefficient (ADC) in the human brain during sleep when compared to the awake state and to determine if they vary across brain regions.

  To assess if there are differences between brain regions.

  end of study

Secondary Outcomes (1)

• To assess inter subject variability in the differences in ADC between awake and sleep.

  End of Study

Study Arms (2)

Phase 2

SHAM COMPARATOR

ADC will be measured in the same subject in the wake state (following a night of regular sleep) and during sleep (following a night of sleep deprivation). The MRI scans will be done in the morning (9-12 pm), once while the subject is sleeping (following a night of sleep deprivation) and once while awake (following regular sleep 9 AM-12 PM).

Other: Brain connectivity and physiology; Other: Brain Wave

Phase I

SHAM COMPARATOR

ADC will be measured in the same subject in the wake state (following a night of regular sleep) and during sleep (following a night of sleep deprivation). The MRI scans will be done in the morning (9 AM-12 pm), once while the subject is sleeping (following a night of sleep deprivation) and once while awake (following regular sleep 9 AM 12 PM).

Other: Brain connectivity and physiology; Other: Brain Wave

Interventions

Brain connectivity and physiology OTHER

Two MRI scanning session will be obtained for each participant both at the same time of day (9AM 12 PM). In one occasion they will be scanned after a night of rested sleep while awake and on another day they will be scanned after one night of sleep deprivation while sleeping in the scanner. In addition to the most sensitive technique selected in the development phase (either DWI or MT), each imaging MRI session will include (1) a resting-state functional connectivity (RSFC; 10 minutes) scan using single-shot T2\*-weighted EPI; and (2) quantitative T1 relaxometry (T1) in a CSF voxel (1mL; cubic) using an inversion recovery experiment with increased interpulse intervals (TI = 200, 300, 400, 500, 700, 1000, 1500, 2000, 3000, 5000, 10000 ms) and a long TR (10000 ms; scan time 2 min) to assess the level of solutes in CSF.

Phase 2; Phase I

Brain Wave OTHER

ECG will be used to monitor heart rate variability (HRV), which differ significantly between the waking state and the different sleep stages

Phase 2; Phase I

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• All Participants
• Between 18 and 60 years of age as determined by self-report.
• Ability to provide written informed consent as determined by physical examination and verbal communication.

You may not qualify if:

• All Participants
• Subjects with self-report of insomnia as determined by self-report and/or medical history;
• 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 C-PAP machine, sleeping during the day, using medication to fall asleep, sleeps less than 6 hours per night, night shift workers), subjects reporting snoring as determined by self-report using STOP-BANG questionnaire for undiagnosed OSA (3 or more yes answers will exclude) and/or medical history;
• Subjects with a history of restless leg syndrome 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, tricyclic antidepressants, selective serotonin reuptake inhibitors \[SSRIs\], or serotonin norepinephrine reuptake inhibitors \[SNRIs\], benzodiazepines and barbiturates) as determined by self-report and/or medical history;
• Current or past DSM-IV or DSM 5 diagnosis of a psychiatric disorder as determined by history and clinical exam including substance use disorder (except for nicotine/caffeine), alcoholism and alcohol dependence. Past history of a mental disorder as defined by DSM IV or DSM 5 will be excluded only if it required hospitalization (any length), or chronic medication management (more than 4 weeks), and that could impact brain function at the time of the study.
• Major medical problems that can impact brain function at the time of the scan (e.g., problems of the CNS including seizures and psychosis; cardiovascular disease including hypertension and arrhythmias; metabolic, autoimmune, endocrine disorders) as determined by self-report, medical history and/or clinical exam.
• Head trauma with loss of consciousness for more than 30 minutes as determined by self-report and/or medical history;
• Positive test for controlled substances (cocaine, methamphetamine, amphetamines, opioids, cannabinoids, benzodiazepines and barbiturates) on any day of study including upon check-in to NIH CC as determined by urine toxicology;
• Pregnant: Females must have negative urine pregnancy test
• 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 3 hours in the MRI scanner as determined by self-report.
• Body weight greater than 250 kg. This is the upper limit that the bed of the MR scanner can accommodate (clinical exam).
• Alcohol consumption on the day of the MRI as determined by breath alcohol test

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

Interventions

Functional Status; Brain Waves

Intervention Hierarchy (Ancestors)

Activities of Daily Living; Rehabilitation; Health Services; Health Care Facilities Workforce and Services; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health; Electroencephalography; Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Electrophysiological Phenomena; Physiological Phenomena; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

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: December 5, 2014
• First Posted: December 8, 2014
• Study Start: July 28, 2015
• Primary Completion: May 11, 2018
• Study Completion: May 11, 2018
• Last Updated: April 29, 2026

Record last verified: 2025-07-29

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)