Alzheimer DiseasePhase 1/2NCT07432997
Pharmacological Enhancement of Glymphatic Function in Humans
A Phase 1/2 study testing Dexmedetomidine and Dexmedetomidine and Midodrine in people with Alzheimer Disease, run by Applied Cognition at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Dexmedetomidine and Dexmedetomidine and Midodrine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Dec 2023to 13 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Participants with urinary retention or requiring to void several times during the night
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Washington State University
Spokane, Washington, 99164
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: The Effect of Dexmedetomidine on Glymphatic Function in the Human Brain
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.
Read the detailed description
Alzheimer's disease (AD) is driven in part by impaired clearance of aggregation-prone proteins, including amyloid-β (Aβ) and tau. Although current disease-modifying therapies primarily target direct protein sequestration, restoration of endogenous waste clearance represents a complementary and underexplored therapeutic strategy. Investigators propose a prospective, interventional study to evaluate whether pharmacologic modulation of sleep-associated glymphatic function enhances clearance of AD-relevant proteins in humans.
In this crossover study, healthy older adults will undergo controlled sleep interventions and receive either a single-agent therapy that suppresses central noradrenergic tone or a fixed-dose combination therapy designed to suppress central noradrenergic tone while stabilizing systemic vascular dynamics. The primary endpoint will be the change in plasma mass-balance indices of Aβ and tau clearance during a standardized overnight intervention.
Investigators hypothesize that coordinated modulation of central noradrenergic signaling and vascular stability will enhance sleep-associated, glymphatic-linked clearance of amyloid and tau. If confirmed, these findings would establish glymphatic modulation as a tractable and druggable systems pathway in humans and support further evaluation of clearance-augmenting strategies as complementary approaches to existing disease-modifying therapies for Alzheimer's disease and related proteinopathies.
- Conditions
- Alzheimer Disease
- Being tested
- Dexmedetomidine, Dexmedetomidine and Midodrine, Placebo
- Keywords
- glymphatic, clearance, increase, drug
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Treatment
Dexmedetomidine and MidodrineDrug
Treatment
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine Cross-Over Placebo | Placebo comparator | Not described Receives: Other: Placebo |
| Dexmedetomidine Cross-Over Treatment | Active comparator | Not described Receives: Drug: Dexmedetomidine |
| Dexmedetomidine & Midodrine Cross-Over Treatment | Active comparator | Not described Receives: Drug: Dexmedetomidine and Midodrine |
| Dexmedetomidine & Midodrine Cross-Over Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine treatment
Measured with mass spectrometry
Measured: Pre/post 4-hour sleep period
Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine and midodrine treatment
Measured with mass spectrometry
Measured: Pre/post 4-hour sleep period
Mean change from baseline in plasma %p-tau217 following dexmedetomidine treatment
Measured with mass spectroscopy
Measured: Pre/post 4-hour sleep period
Mean change from baseline in plasma %p-tau217 following dexmedetomidine and midodrine treatment
Measured with mass spectroscopy
Measured: Pre/post 4-hour sleep period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study start11 Dec 2023
- Primary completion13 Sep 2024
- Study completion13 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Applied Cognition
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Stanford University, Washington State University
- Responsible party
- Sponsor
- Investigators
- Paul Dagum, MD PhD, Study director, Applied CognitionAlbert Cheung, MD, Principal investigator, Stanford HospitalBrieann C Satterfield, PhD, Principal investigator, Washington State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07432997
- Sponsor's protocol ID
- AC.2023.01
- Status last verified
- Feb 2026
- First submitted
- 15 Feb 2026
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dexmedetomidine on Glymphatic Function in the Human Brain
- ClinicalTrials.gov ID
- NCT07432997
- Acronym / sponsor ID
- AC.2023.01
- Conditions
- Alzheimer Disease
- Keywords
- glymphatic, clearance, increase, drug
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Applied CognitionIndustry (pharma, biotech, devices)
- Collaborators
- Stanford University, Washington State University
- Study start
- 11 Dec 2023 (actual)
- Primary completion
- 13 Sep 2024 (actual)
- Study completion
- 13 Sep 2024 (actual)
- First posted
- 25 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Alzheimer's disease (AD) is driven in part by impaired clearance of aggregation-prone proteins, including amyloid-β (Aβ) and tau. Although current disease-modifying therapies primarily target direct protein sequestration, restoration of endogenous waste clearance represents a complementary and underexplored therapeutic strategy. Investigators propose a prospective, interventional study to evaluate whether pharmacologic modulation of sleep-associated glymphatic function enhances clearance of AD-relevant proteins in humans.
In this crossover study, healthy older adults will undergo controlled sleep interventions and receive either a single-agent therapy that suppresses central noradrenergic tone or a fixed-dose combination therapy designed to suppress central noradrenergic tone while stabilizing systemic vascular dynamics. The primary endpoint will be the change in plasma mass-balance indices of Aβ and tau clearance during a standardized overnight intervention.
Investigators hypothesize that coordinated modulation of central noradrenergic signaling and vascular stability will enhance sleep-associated, glymphatic-linked clearance of amyloid and tau. If confirmed, these findings would establish glymphatic modulation as a tractable and druggable systems pathway in humans and support further evaluation of clearance-augmenting strategies as complementary approaches to existing disease-modifying therapies for Alzheimer's disease and related proteinopathies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 55 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- Potential participants who meet any of the following criteria will be excluded from participating in the study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineTreatment | Drug | Dexmedetomidine Cross-Over Treatment |
| Dexmedetomidine and MidodrineTreatment | Drug | Dexmedetomidine & Midodrine Cross-Over Treatment |
| PlaceboPlacebo | Other | Dexmedetomidine & Midodrine Cross-Over Placebo, Dexmedetomidine Cross-Over Placebo |
Primary outcome
Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine treatment
Time frame: Pre/post 4-hour sleep period
Measured with mass spectrometry
Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine and midodrine treatment
Time frame: Pre/post 4-hour sleep period
Measured with mass spectrometry
Mean change from baseline in plasma %p-tau217 following dexmedetomidine treatment
Time frame: Pre/post 4-hour sleep period
Measured with mass spectroscopy
Mean change from baseline in plasma %p-tau217 following dexmedetomidine and midodrine treatment
Time frame: Pre/post 4-hour sleep period
Measured with mass spectroscopy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Dagum, MD PhD study director
Applied Cognition
Albert Cheung, MD principal investigator
Stanford Hospital
Brieann C Satterfield, PhD principal investigator
Washington State University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dexmedetomidine and Dexmedetomidine and Midodrine in people with Alzheimer Disease, run by Applied Cognition at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change from baseline in plasma Aβ42/Aβ40 ratio following dexmedetomidine treatment (time frame: Pre/post 4-hour sleep period). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.