Influence of Dexmedetomidine on the Human Glymphatic Cerebrospinal Fluid Flow, Neural Activity and Cerebral Blood Flow in Functional Magnetic Resonance Imaging (GlymphDex)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helsinki University Central Hospital

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Decision date (initial)

2023-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Acta Anaesthesiologica Scandinavica Foundation; Finnish State Funding for Research

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The aim of this study is to characterize brain pulsations, blood flow, and cerebrospinal fluid flow using functional MRI in different states of consciousness and couple these to neural activity in electroencephalography in the awake brain and under different levels of dexmedetomidine sedation.

Secondary objectives 1

1. The secondary objective is to create a model for glymphatic flow in functional MRI.

Conditions and MedDRA coding

Neurodegenerative disease; Delirium; Acute neurological disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Fluent Finnish skills
2. Age 18-45 years
3. Healthy
4. Normal baseline ECG
5. Normal blood pressure
6. Normal SpO2
7. No signs of substance abuse
8. Acceptable values in laboratory tests
9. Normal weight (BMI 18.5-30 kg/m2)
10. Head circumference max 59 cm
11. Right-handedness

Exclusion criteria 19

1. Previous history of intolerance to the study drug or related compound/additive
2. Strong susceptibility to allergic reactions
3. Known history of significant anaesthetic complication
4. Strong susceptibility to nausea
5. Airway management is evaluated difficult
6. Gastroesofageal reflux
7. Pregnancy, planned pregnancy, or lactation
8. Existing regular medication (incl contraception)
9. Participation in any other clinical study involving investigational or marketed drug products concomitantly or within 3 months prior to entry to this study
10. Blood donation within 3 months prior to and during the study
11. Known history of snoring or obstructive sleep apnea
12. Chronic sleep disturbance
13. Previous or present alcoholism or drug abuse or tendency to drug or alcohol abuse
14. Low body weight (< 50 kg) or BMI < 18.5 kg/m2 or BMI > 30 kg/m2
15. Smoking during one month before the study or during the study
16. Inability or difficulty of lying or sleeping in horizontal supine position
17. Forearm veins evaluated difficult to cannulate
18. Any contraindication to MRI
19. Tinnitus or hearing impairment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is the change in functional magnetic resonance signals or power spectra reflecting neural activity, brain pulsation, cerebral blood flow, and CSF flow with changing states of consciousness.

Secondary endpoints 6

1. • Change in any MRI signal with drug concentrations, different states of consciousness, sedation-related EEG changes, and blood biomarkers.
2. • Influence of physiological parameters on MRI signals, biomarkers, and EEG.
3. • Comparison of regional and tissue specific differences in MRI between different states of consciousness and with different levels of sedation.
4. • Correlation between MRI data, EEG data and peripheral blood biomarkers with sleep quality on the previous night.
5. • Correlation of dexmedetomdine sedation with levels of biomarkers, particularly plasma sodium, plasma osmolality, blood glucose, serum insulin, plasma copeptin and serum cortisol levels.
6. • Creating a model for glymphatic CSF flow in functional MRI (i.e. typical functional MRI signal/spectra).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helsinki University Central Hospital

Sponsor organisation

Helsinki University Central Hospital

Address

Haartmaninkatu 8

City

Helsinki

Postcode

00290

Country

Finland

Scientific contact point

Organisation

Helsinki University Central Hospital

Contact name

Terhi Lohela

Public contact point

Organisation

Helsinki University Central Hospital

Contact name

Terhi Lohela

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications