Clinical trial NCT04255758: Acute Effects of Vigorous-intensity Aerobic Exercise on Glymphatic Flow in Healthy Adults
Official title: Academic Investigational Study of Acute Effects of Vigorous-intensity Aerobic Exercise on Glymphatic Flow in Healthy Adults
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Glymphatic System
Neurodegeneration
Keywords: glymphatic system
cerebral perfusion
aerobic exercise
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
First posted: 2020-02-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective interventional study model, all subjects undergo the same exercise intervention and results are compared to baseline values
Primary purpose: BASIC_SCIENCE

Brief summary: This study investigates changes in glymphatic flow in the brain acutely after vigorous-intensity steady-state aerobic exercise. Twenty subjects (10 male and 10 female) perform 25 minute submaximal cycle ergometry exercise and the changes in the glymphatic flow and cerebral perfusion are evaluated using a variety of MRI sequences (e.g. MREG).

Detailed description: The glymphatic system is a drainage system for the brain to help maintain fluid balance and extract waste metabolites. Glymphatic system function (healthy glymphatic flow) may prevent accumulation of harmful substances and therefore slow down the onset of neurodegenerative diseases.

The hypothesis is, that glymphatic flow could be increased through exercise and enhanced cerebral arterial pulsality, which might explain some of the brain health benefits of exercise proven in epidemiological studies. This study indirectly investigates the acute changes in the glymphatic flow acutely after aerobic exercise using MREG that measures pulse wave propagation as an indirect surrogate marker for glymphatic flow.

Twenty healthy subjects (n=20, 10 male, 10 female, age 18-45 years) will perform 25 minute 70%VO2max cycle ergometry exercise. The glymphatic flow and cerebral perfusion will be measured using magnetic resonance imaging sequences before and after exercise. The glymphatic flow is measured using 10 Hz fMRI technique called magnetic resonance encephalography (MREG). In addition, perfusion MRI is used to evaluate changes in brain perfusion.

Eligibility criteria: Inclusion Criteria:

* Age 18-45
* BMI 18-30
* Resting Blood pressure \< 140/90 mmHg

Exclusion Criteria:

* History of a cardiac event
* Insulin or medically treated diabetes
* Any chronic disease or condition that could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
* Presence of ferromagnetic objects that would make MR imaging contraindicated
* Claustrophobia
* Abundant use of alcohol
* Use of narcotics
* Smoking of tobacco or consuming snuff tobacco
* Diagnosed depressive or bipolar disorder
* Abnormalities in resting ECG (revised by the study physician)
* Pregnancy

Primary outcomes:
measure: MREG cardiovascular pulse wavefront
timeFrame: 3 hours
Secondary outcomes:
measure: Cerebral perfusion fMRI
timeFrame: 3 hours
measure: Heart rate (HR)
timeFrame: 3 hours
measure: Blood pressure (BP)
timeFrame: 3 hours
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku PET Centre
Study officials:
affiliation: Turku PET Centre
name: Ilkka Heinonen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rajna Z, Raitamaa L, Tuovinen T, Heikkila J, Kiviniemi V, Seppanen T. 3D Multi-Resolution Optical Flow Analysis of Cardiovascular Pulse Propagation in Human Brain. IEEE Trans Med Imaging. 2019 Sep;38(9):2028-2036. doi: 10.1109/TMI.2019.2904762. Epub 2019 Mar 15.
citation: von Holstein-Rathlou S, Petersen NC, Nedergaard M. Voluntary running enhances glymphatic influx in awake behaving, young mice. Neurosci Lett. 2018 Jan 1;662:253-258. doi: 10.1016/j.neulet.2017.10.035. Epub 2017 Oct 25.