Acute Effects of Vigorous-intensity Aerobic Exercise on Glymphatic Flow in Healthy Adults (GLYMREG)

Academic Investigational Study of Acute Effects of Vigorous-intensity Aerobic Exercise on Glymphatic Flow in Healthy Adults

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).

Study Overview

• Status: Unknown
• Conditions: Glymphatic System; Neurodegeneration
• Intervention / Treatment: Other: Cycle Ergometer Exercise

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ilkka Heinonen, PhD; Phone Number: +358 408 393 962; Email: ilkka.heinonen@utu.fi

Study Locations

• Finland
  • Turku, Finland, 20521
    • Recruiting
    • Turku PET Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vigorous-intensity Aerobic Exercise; Vigorous-intensity aerobic exercise, single intervention	Other: Cycle Ergometer Exercise; 25 minutes, 70% VO2max steady state cycle ergometry exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MREG cardiovascular pulse wavefront	Is processed into three-dimensional vector fields and used as an assessment of glymphatic flow, scanned once before and multiple times after exercise intervention in 5-minute sequences	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral perfusion fMRI	5-minute MR imaging sequences evaluating changes in blood flow, scanned once before and multiple times after exercise intervention	3 hours
Heart rate (HR)	Wearable heart rate monitoring, measures heart beats per second, continuous throughout the study	3 hours
Blood pressure (BP)	Blood pressure monitoring, evaluates systolic and diastolic pressures (mmHg) continuous throughout the study	3 hours

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Ilkka Heinonen, PhD, Turku PET Centre

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 8, 2021
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (ACTUAL): February 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: aerobic exercise; glymphatic system; cerebral perfusion
• Additional Relevant MeSH Terms: Pathologic Processes; Nerve Degeneration
• Other Study ID Numbers: T6/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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