Pharmacological Enhancement of Glymphatic Function in Humans

NCT07432997 | Completed Phase 1

• 1 other identifier: AC.2023.01
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

Alzheimer's disease is linked in part to the buildup of harmful proteins in the brain, including amyloid and tau. Most current treatments aim to remove these proteins directly. This study explores a different approach: helping the brain clear waste more effectively during sleep. The investigators will test whether certain medications can safely boost the brain's natural "cleaning system," known as the glymphatic system, in healthy older adults. Participants will receive controlled sleep treatments and blood tests to measure protein clearance. If successful, this strategy could support new therapies that work alongside existing Alzheimer's treatments.

Conditions

Alzheimer Disease

Keywords

glymphatic; clearance; increase; drug

Outcome Measures

Primary Outcomes (4)

• Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine treatment

  Measured with mass spectrometry

  Pre/post 4-hour sleep period

• Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine and midodrine treatment

  Measured with mass spectrometry

  Pre/post 4-hour sleep period

• Mean change from baseline in plasma %p-tau217 following dexmedetomidine treatment

  Measured with mass spectroscopy

  Pre/post 4-hour sleep period

• Mean change from baseline in plasma %p-tau217 following dexmedetomidine and midodrine treatment

  Measured with mass spectroscopy

  Pre/post 4-hour sleep period

Study Arms (4)

Dexmedetomidine Cross-Over Placebo

PLACEBO COMPARATOR

Other: Placebo

Dexmedetomidine Cross-Over Treatment

ACTIVE COMPARATOR

Drug: Dexmedetomidine

Dexmedetomidine & Midodrine Cross-Over Treatment

ACTIVE COMPARATOR

Drug: Dexmedetomidine and Midodrine

Dexmedetomidine & Midodrine Cross-Over Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Dexmedetomidine DRUG

Treatment

Dexmedetomidine Cross-Over Treatment

Dexmedetomidine and Midodrine DRUG

Treatment

Dexmedetomidine & Midodrine Cross-Over Treatment

Placebo OTHER

Placebo

Dexmedetomidine & Midodrine Cross-Over Placebo; Dexmedetomidine Cross-Over Placebo

Eligibility Criteria

• Age: 55 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Potential participants must satisfy the following criteria to be enrolled in the study:
• In the opinion of the Principal Investigator, participants must be fluent in English and be able to understand the informed consent form approved by the Institutional Review Board (IRB). All participants must sign the study informed consent document indicating that they understand the purpose of procedures required for the study and are willing to participate in the study prior to any study procedures being performed.
• Participants may be men or women, age 55 - 65 years (inclusive). Enrollment will target equal number of men and women participants.
• Participants must have a MoCA score at least 26 for in-person assessment or 19 for over-the-phone assessment, unless waived by decision of the PI.
• Participants must have a GDS-15 score of 4 or less.
• Participants must provide an address and phone number where they can be accessible to the Study team for follow up.
• Participants must agree to wear the GF Monitor per the Study Phase under baseline and dexmedetomidine infusion and be willing to complete all other aspects of the protocol.

You may not qualify if:

• Potential participants who meet any of the following criteria will be excluded from participating in the study:
• Participants with a formal diagnosis of any sleep disorder (e.g., sleep apnea on PAP therapy, insomnia, restless leg syndrome, circadian rhythm sleep disorder, parasomnia).
• Participants with a history of significant neurological disease or history of epilepsy.
• Participants with cardiovascular disease or hypertension.
• Participants with diabetes.
• Participants with traumatic brain injury, or serious mental illness including bipolar disorder, schizophrenia, major depressive disorder or post-traumatic stress disorder.
• Participants who have taken in the past 30 days prescribed or over-the-counter (OTC) stimulants, sleeping medications, or psychiatric medications including antidepressants.
• Participants who consume more than 400 mg/day of caffeine. Participants will be required to not consume caffeine on the day-of the sleep study.
• 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.
• Participants who are enrolled in other research studies and are receiving an investigational drug within 30 days of the planned start date for visit 1.
• Participants who have any condition that, in the opinion of the Principal Investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements.
• Participants who have a pre-planned surgery or medical procedure that would interfere with the conduct of the study.
• Participants with a serious infection requiring medical attention in the past 30 days.
• Any significant neurological impairment in the opinion of the Principal Investigator that would affect the GF Monitor data.
• Participants with a diagnosis of substance use-disorder in the past 2 years.

Sponsors & Collaborators

• Applied Cognition: lead
• Stanford University: collaborator
• Washington State University: collaborator

Study Sites (2)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Washington State University

Spokane, Washington, 99164, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Dexmedetomidine; Midodrine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Paul Dagum, MD PhD

  Applied Cognition

  STUDY DIRECTOR

• Albert Cheung, MD

  Stanford Hospital

  PRINCIPAL INVESTIGATOR

• Brieann C Satterfield, PhD

  Washington State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The laboratory assessing the blood-based biomarker results was masked to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2026
• First Posted: February 25, 2026
• Study Start: December 11, 2023
• Primary Completion: September 13, 2024
• Study Completion: September 13, 2024
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)