Exploring the Link Between Sleep and Brain Clearance (BBCDS)

Biomarkers of Brain Clearance During Sleep

The purpose of this study is to assess the link between sleep and the clearance of waste products from the brain. This will be assessed in a group of healthy older adults.

Study Overview

• Status: Enrolling by invitation
• Conditions: Healthy Aging
• Intervention / Treatment: Behavioral: Auditory Stimulation; Behavioral: Sham (no stimulation)

Detailed Description

First, the investigators want to assess the relationship between sleep parameters and markers for brain clearance, assessed with MRI and blood samples. Second, the investigators want to probe whether associations can be influenced by modulation of sleep parameters by means of auditory stimulation.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland
    • Institute for Regenerative Medicine, University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participation in previous longitudinal cohort studies at the study site
• Ability to provide written and verbal informed consent
• Fluency in the German language
• Stable home situation that allows for reliable application of the intervention for the duration of the study
• Ability to apply the intervention for the duration of the study, either alone or with support from a co-habitant
• For women: Hormonal contraception, if menstrual cycle is still present or has been present within a year
• Good general health status, normal cognitive function

Exclusion Criteria:

• Failure or inability to give informed consent
• Inability to follow the procedures of the investigation
• For women: pregnancy or breastfeeding
• Presence of sleep disorders (e.g. sleep apnoea, narcolepsy, restless leg syndrome, insomnia, REM sleep disorder)
• Shift-work or a home situation that requires several awakenings during the night (e.g. newborn)
• History of serious illness likely to interfere with study outcomes
• Presence or history of a diagnosed neuropsychiatric illness
• Current diagnosis of uncontrolled or poorly controlled diabetes
• Current cancer of the brain or unstable cancer undergoing treatment
• Evidence of serious atherosclerotic cardiovascular disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Auditory Stimulation; Auditory Stimulation during sleep	Behavioral: Auditory Stimulation; enhancement of sleep slow wave activity through acoustic stimulation
Sham Comparator: No Auditory Stimulation; Playing no tones during sleep but still recording brain activity	Behavioral: Sham (no stimulation); Playing no tones during sleep but still recording brain activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlation between EEG slow wave activity (uV) and cerebrospinal fluid flow (ml/min) from phase contrast MRI	2 weeks
Correlation between EEG slow wave activity (uV) and diffusivity (mm2/s) from diffusion MRI	2 weeks
Correlation between EEG slow wave activity (uV) and perfusion (ml/min/100 ml) from arterial spin labelling MRI	2 weeks
Correlation between EEG slow wave activity (uV) and beta-amyloid (pg/ml)	2 weeks
Correlation between EEG slow wave activity (uV) and tau (pg/ml)	2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between EEG slow wave activity (uV) and fatigue, assessed via the fatigue severity scale (FSS) questionnaire	2 weeks
Correlation between EEG slow wave activity (uV) and sleepiness, assessed with the Epworth Sleepiness Scale questionnaire	2 weeks
Correlation between EEG slow wave activity (uV) and memory function, assessed with the Hopkins Verbal Learning Test (memory score)	2 weeks
Correlation between EEG slow wave activity (uV) and attention, assessed with the Trail Making Test (time to completion)	2 weeks
Correlation between EEG slow wave activity (uV) and C-Reactive Protein (mg/L), assessed from a blood sample	2 weeks
Correlation between EEG slow wave activity (uV) and TNF-alpha (pg/L), assessed from a blood sample	2 weeks
Correlation between EEG slow wave activity (uV) and interleukins (pg/L), assessed from a blood sample	2 weeks
Correlation between EEG slow wave activity (uV) and executive function (summary score, dimensionless)	2 weeks
Correlation between EEG slow wave activity (uV) and neuro-metabolite levels (mmol) from magnetic resonance spectroscopy	2 weeks

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Anton Gietl, Institute for Regenerative Medicine, University of Zurich

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): July 1, 2026

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: BBCDS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No