Effects of Sleep Deprivation and Adrenergic Inhibition on Glymphatic Flow in Humans

• Status: Completed
• Trial end date: 2019-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The project is aimed at identifying how the adrenergic antagonist 'carvedilol' modulates the effects of sleep deprivation in healthy volunteers. The study is a double-blind, randomized, placebo-controlled, cross-over study. Investigators will include 20 healthy volunteers who will undergo three functional magnetic resonance (fMRI) imaging sessions, one at baseline, and two after sleep deprivation (one night without sleep). The two sleep-deprivation scans are performed in a randomized order where subjects receive placebo or carvedilol, in a within-subject, cross-over study design.

The following domains will be described: 1) fMRI imaging of cerebrospinal fluid (CSF) pulsations (glymphatic flow) in the human brain, performed by a combination of fMRI protocols that includes structural (T1, T2, diffusion weighted) and functional (multiband/fast imaging, spectroscopy) imaging. 2) fMRI imaging during wakefulness and sleep are determined by simultaneous electroencephalographic (EEG) recordings. 3) The effects of sleep deprivation on the fMRI derived glymphatic flow signal. 4) The effects of the adrenergic antagonist carvedilol on fMRI measurements and sleep intensity. 5) Quantification of cognitive performance before and after a nap in the MRI. Cognitive testing includes: assessments of visual attention, reaction time, paired-associative memory, working memory, emotional recognition and subjective ratings of sleepiness and mood.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Gitte Moos Knudsen
• Collaborators: Center for translational Neuroscience, University of Copenhagen, Denmark; Danish Center for Sleep Medicine; Danish Center for Sleep Medicine, Rigshospitalet, Denmark
• Treatments: Adrenergic Agents; Carvedilol

Criteria

Inclusion Criteria:

• Healthy volunteer (male or female) between 18 and 35 years.

• Good sleeper with sleep efficiency above 80%.

Exclusion Criteria:

• Current or former primary psychiatric disorder in volunteer of first degree relatives (DSM IV Axis I or WHO ICD-10 diagnostic classification).

• Current or previous neurological disease, severe somatic disease, or the consumption of drugs likely to influence the test results.

• Claustrophobia or fear of being in an MR-scanner.

• Alcohol or drug abuse.

• Regular smoking or nicotine addiction

• Extreme morning or evening type, or extreme short or long sleeper.

• Disordered sleep, regular shift-work or extreme tiredness (e.g. Epworth Sleepiness Scale (ESS) > 10).

• Crossing of multiple time zones within the last 6 months.

• Extreme use of stimulants such as caffeine.

• Not adhering to the prescribed sleep-wake schedule before study initiation.

• Left handedness.

• Obesity (BMI > 27.5).

• Non-fluent in Danish or pronounced visual or auditory impairments.

• Current or past learning disability.

• Large head size (>59 cm in circumference).

• Pregnancy

• Contraindications for MRI (pacemaker, metal implants, etc.).

• Allergy to the ingredients in the administered drug.

• Abnormal ECG (e.g. prolonged QT syndrome, etc.)

• Dizzy when changing from supine to upright position (e.g. postural orthostatic tachycardia syndrome).

• Mild hypotension (blood pressure below 100/70 mmHg)

• Hypertension (blood pressure above 140/90 mmHg).