Applied Cognition Benchmarking Study

Healthy Clinical Trial

— BRAIN3  

Official title:

Measuring and Monitoring Brain Health in Older Adults: The Applied Cognition Glymphatic Function Study at The Villages

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06222385
• Other study ID #: AC.2022.02
• Status: Completed
• Phase: N/A
• Start date: November 7, 2022
• Est. completion date: June 8, 2023

Study information

• Verified date: January 2024
• Source: Applied Cognition
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a cross-over randomized study to validate the Sponsor investigational medical device against measurements of glymphatic function from MRI-based neuroimaging, EEG, blood biomarkers and cognitive tests in healthy older volunteers.

Description:

The study population will consist of healthy individuals, ages 55 to 65, that are cognitively normal and do not have a medical history of neurological or sleep disorder, cardiovascular disease, hypertension, or diabetes. The objectives of this study are to define whether sleep- and wake-associated device measurements (i) faithfully reflect glymphatic function measured by gold-standard contrast enhanced MRI and non-invasive MRI-based measures of glymphatic function; (ii) replicate pre-clinical findings between sleep EEG power bands and glymphatic flow; (iii) predict plasma levels of Alzheimer's disease (AD)-related biomarkers; and (iv) predict morning cognitive performance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Participants must have a Montreal Cognitive Assessment (MoCA) score at least 26.

2. Participants must have a Geriatric Depression Scale (GDS) 15-item score of 4 or less.

Exclusion Criteria:

1. Participants with a formal diagnosis of any sleep disorder (e.g., sleep apnea on positive-airway-pressure (PAP) therapy, insomnia, restless leg syndrome, circadian rhythm sleep disorder, parasomnia).

2. Participants with a history of significant neurological disease or history of epilepsy.

3. Participants with cardiovascular disease or cardiovascular risk factors (smoking or hypertension).

4. Participants with diabetes.

5. Participants with traumatic brain injury, or serious mental illness including bipolar disorder, schizophrenia, major depressive disorder or post-traumatic stress disorder.

6. Participants who have taken in the past 30 days prescribed or overthe- counter (OTC) stimulants, sleeping medications, or psychiatric medications including antidepressants.

7. Participants who consume more than 400 mg/day of caffeine. Participants will be required to not consume caffeine beginning 12pm on the day-of the sleep study.

8. Female Participants who consume more than 3 alcoholic drinks on any day or more than 7 drinks per week. Male participants who consume more than 4 alcoholic drinks on any day or more than 14 drinks per week.

9. Participants planning travel to alternate time zones within two weeks of study participation

10. Participants with travel plans or conflicts that would prevent them from either Study Visit.

11. Participants who are enrolled in other research studies and are receiving an investigational drug within 30 days of the planned start date.

12. Participants who have any condition that, in the opinion of the Sponsor Principal Investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements.

13. Participants with absolute or relative contraindications to MRI imaging based on current up-to-date screening questionnaires including claustrophobia, inability to lie still on their back for 30-45 minutes or require sedation prior to the MRI.

14. Participants with a head circumference greater than 60 cm that would prevent use of a high-resolution 64 channel MRI head coil required for this study

15. Participants who have a pre-planned surgery or medical procedure that would interfere with the conduct of the study.

16. Participants who have an implanted medical device or contraindications that would exclude MRIs

17. Participants with a serious infection requiring medical attention in the past 30 days

18. Participants with a diagnosis of substance use-disorder in the past 2 years.

19. Participants with known acute or chronic kidney disease and/or compromised GFR.

Related Conditions & MeSH terms

• Healthy

Intervention

Diagnostic Test:
• Device measurements during overnight sleep and morning wake
Overnight period and morning period device measurements
• Device measurements during overnight wake and morning sleep
Overnight period and morning period device measurements

Locations

Country	Name	City	State
United States	UF Health - Precision Health Research Center	The Villages	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Applied Cognition	University of Florida Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contrast-enhanced MRI	Overnight sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by ROI parenchymal signal intensity using gold-standard contrast-enhanced MRI for gray and white matter ROI.	Immediately after the overnight sleep/wake period
Primary	Non-invasive MRI - diffusion-based intravoxel incoherent motion	Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using diffusion-based intravoxel incoherent motion (IVIM)-MRI (long-distance water transport) (diffusion signal, a.u.).	Immediately before and immediately after each sleep/wake period
Primary	Non-invasive MRI - fast functional MRI	Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using fast functional MRI (f-MRI) low-frequency vasomotor oscillations, Hz.	Immediately before and immediately after each sleep/wake period
Primary	Non-invasive MRI - T1/FLAIR-based assessment	Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using T1/FLAIR-based assessment of MRI-visible perivascular spaces (MVPVS) that are structural indicators of perivascular impairment, (a.u.).	Immediately before and immediately after each sleep/wake period
Primary	Non-invasive MRI - multi-echo arterial spin-labeling	Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using multi-echo arterial spin-labeling (ME-ASL)-MRI (glial-vascular water transport) (flow in ml/sec).	Immediately before and immediately after each sleep/wake period
Primary	Non-invasive MRI - phase-contrast	Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic function measured by non-invasive MRI measures of glymphatic function using phase-contrast (PC)-MRI (aqueductal cerebral spinal fluid (CSF) flow) (flow in ml/sec).	Immediately before and immediately after each sleep/wake period
Secondary	Sleep EEG	Device overnight sleep measurements (impedances in milli-ohms) correlations with overnight recorded sleep EEG power bands (relative delta, theta, alpha and beta power in %) and heart rate replicate pre-clinical correlations of glymphatic flow (measured using 2-photon microscopy in a.u.) with EEG power bands (relative delta, theta, alpha and beta power in %) and heart rate.	Measurements sampled every 5 to 10 minutes during the overnight sleep period
Secondary	Blood biomarkers	Sleep- and wake-associated device measurements (impedances in milli-ohms) faithfully reflect glymphatic clearance measured by amyloid beta40, beta42, n-tau 181, n-tau 217, p-tau 181, p-tau 217 blood biomarkers	Immediately before and immediately after each sleep/wake period
Secondary	Cognitive function - trail making tests A&B	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on Trail Making Tests A&B (time in seconds).	Immediately after the sleep/wake period
Secondary	Cognitive function - symbol digit modality test	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on symbol digit modality test (SDMT) (number correct).	Immediately after the sleep/wake period
Secondary	Cognitive function - psychomotor vigilance test	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on psychomotor vigilance test (PVT) (mean and standard deviation of reaction time).	Immediately after the sleep/wake period
Secondary	Cognitive function - digits forward recall	Overnight sleep- and wake-associated device measurements predict morning cognitive performance based on digits forward recall (maximum number of correctly recalled digits).	Immediately after the sleep/wake period