Alzheimer Disease, Late OnsetEarly Phase 1ALPSNCT05138848
Time-in-bed Restriction in Older Adults With Sleep Difficulties With and Without Risk for Alzheimer's Disease
A Early Phase 1 study testing Time in Bed Restriction and Sleep Schedule in people with Alzheimer Disease, Late Onset and Mild Cognitive Impairment, run by University of Pittsburgh at 1 site in United States.
Trial summary
Dementia caused by Alzheimer's disease affects approximately 5.6 million adults over age 65, with costs expected to rise from $307 billion to $1.5 trillion over the next 30 years. Behavioral interventions have shown promise for mitigating neurodegeneration and cognitive impairments. Read more about this study
- Who is it for?
- Ages 65 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Late Onset, Mild Cognitive Impairment, Sleep
- What is being tested?
- Time in Bed Restriction and Sleep Schedule
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2022to 30 Jun 2026
- Phase
- Early Phase 1
- 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 65 to 85 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Age 65-85.
- Self-report mean sleep efficiency (the time in bed spent asleep within the time of lights out to final awakening) < 90% based on diary and actigraphy estimates and wake time after sleep onset > 20 minutes based on diary and actigraphy estimates.
- Self-reported normal or corrected-to-normal visual and auditory acuity.
Who cannot join
- Shift work involving night shift or regular work within the hours of 12am and 6am.
- Presence of a chronic condition that significantly affects sleep.
- Severe psychiatric condition including major depressive disorder, panic disorder, substance use disorders, and alcohol abuse/dependence within the past 6 months, or a lifetime history of a psychotic disorder or bipolar I disorder, based on initial online/phone self-report diagnoses, and subsequently based on a structured psychiatric interview.
- Current use of medications affecting sleep such as antidepressants, antipsychotic medications, anticonvulsants, and steroids.
- Current use of sedating drugs used at bedtime.
- Consumption of > 14 alcohol drinks per week or > 6 drinks at a single sitting.
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- Consumption of > 3 caffeine drinks per day.
- Prior diagnosis of a Central nervous system (CNS) disease, such as multiple sclerosis, stroke, Parkinson's disease, Alzheimer's disease, seizure disorder, delirium or dementia, a loss of consciousness > 24 hours, or traumatic brain injury as identified by the Cumulative Illness Rating Scale for Geriatrics (CIRS). Participants who are diagnosed with Alzheimer's disease based on neuropsychological testing will be excluded.
- Sleep efficiency > 90% and wake time after sleep onset < 20 minutes consistent with the rationale of the inclusion criteria described above.
- Apnea/hypopnea index greater than 15 as determined by one night of Apnea Link Plus screening.
- Metal in the body. Rationale: Due to the nature of magnetic resonance imaging (MRI), participants cannot have any metal implants in their bodies, cannot have worked in a metal shop or been exposed to metal fragments during combat. Metal dental work (e.g. fillings crowns) may be allowed if compatible with the fMRI scanner.
- Claustrophobia. Rationale: Could prevent the participant from completing the MRI scans.
- Severe obesity. BMI > 40. Rationale: Could prevent the participant from completing the MRI scan.
- Near-miss or prior automobile accident "due to sleepiness" within the past 12 months. Rationale: reduces the risk of sleepiness-related accidents.
- Employed as a commercial driver during the study (for example, bus drivers, train engineers, airplane pilots). Rationale: reduces the risk of sleepiness-related accidents.
- A score below 23 on the Telephone Interview for Cognitive Status. Rationale: This cut-off has been demonstrated to differentiate well between individuals with mild cognitive impairment from individuals with dementia who would have decision making impairments (Seo et al. 2011, Archives of Gerontology and Geriatrics). This ensures that decision making abilities are intact.
- An Epworth sleepiness score greater than 10. Rationale: ensures that sleepiness is not excessive before starting the intervention that could further increase sleepiness. (Mazzotti, Diego R., et al. "Is the Epworth Sleepiness Scale sufficient to identify the excessively sleepy subtype of OSA?." Chest 161.2 (2022): 557-561; Aurora, R. Nisha, et al. "Correlating subjective and objective sleepiness: revisiting the association using survival analysis." Sleep 34.12 (2011): 1707-1714.)
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Western Psychiatric Hospital
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Slow-wave Sleep Enhancement in Those at Risk for Alzheimer's Disease: Links With Memory, Excitotoxicity, and Plasma A-beta
Dementia caused by Alzheimer's disease affects approximately 5.6 million adults over age 65, with costs expected to rise from $307 billion to $1.5 trillion over the next 30 years. Behavioral interventions have shown promise for mitigating neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition and deteriorates with advancing age and Alzheimer's disease. Thus, it is a priority to examine whether improving sleep modifies Alzheimer's disease pathophysiology and cognitive function. Extant research suggests that deeper, more consolidated sleep is positively associated with memory and executive functions and networks that underlie these processes. Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus during sleep may help to preserve the long-range connections that support memory and cognitive function. In pre-clinical Alzheimer's disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown to leave neurons vulnerable to further amyloid deposition. Synaptic downscaling through SWA may mitigate the progression of Alzheimer's disease through these pathways. The proposed study will behaviorally increase sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on amyloid deposition and multiple factors associated with Alzheimer's disease risk. This study will examine whether behaviorally enhanced SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal connectivity, plasma amyloid levels, and cognitive function. This research addresses whether a simple, feasible, and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity, Alzheimer's pathophysiology, and cognitive performance.
- Conditions
- Alzheimer Disease, Late Onset, Mild Cognitive Impairment, Sleep, Cognitive Change, Amyloid
- Being tested
- Time in Bed Restriction, Sleep Schedule
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Time in Bed RestrictionBehavioural
Participants will undergo a 4-week sleep intervention that includes specified in- and out-of-bed times as well as a restriction to their habitual time in bed (average sleep opportunity including naps). This will be truncated equally at the beginning and end of the night.
Sleep ScheduleBehavioural
Participants will maintain their typical sleep schedule for 4-weeks.
| Study group | Role | What they receive |
|---|---|---|
| Time in Bed Restriction | Experimental | Time in Bed (TIB) restriction of 85% of habitual TIB. Receives: Behavioral: Time in Bed Restriction; Behavioral: Sleep Schedule |
| Control | Active comparator | Participants will follow their typical sleep schedule consistent with measured average sleep and wake times. Receives: Behavioral: Sleep Schedule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in slow-oscillation activity assessed with electroencephalography
Slow oscillation electroencephalographic power (0.5-1 Hz) during non-rapid eye movement sleep
Measured: Baseline and 4 weeks
Mean change in Hippocampal Activation
Change in mean percent signal change of the hippocampus during memory encoding assessed with functional magnetic resonance imaging
Measured: Baseline and 4 weeks
Change in mean Plasma amyloid-beta 1-42
Change in mean amyloid-beta detected in the plasma in the morning
Measured: Baseline and 4 weeks
Overnight memory retention on the AB paired associate task
Mean change in percent correct memory
Measured: Baseline and 4 weeks
Secondary outcomes (13)
Mean change in delta activity during sleep
Mean change in delta electroencephalographic power (1-4 Hz) during non-rapid eye movement sleep
Measured: Baseline and 4 weeks
Amyloid positivity status
Amyloid positivity above or below established cutoffs assessed with Pittsburgh Compound B positron emission tomography
Measured: Baseline
Mean change in Sleep Efficiency
Mean change in the proportion of time in bed spent sleeping
Measured: Baseline and 4 weeks
Mean percent signal change in medial prefrontal activation
Mean percent signal change in medial prefrontal cortex activation during a memory encoding task
Measured: Baseline and 4 weeks
Medial prefrontal-Hippocampal Connectivity
Change in the correlation between medial prefrontal activity and hippocampal activity during memory encoding assessed with functional magnetic resonance imaging during awake rest
Measured: Baseline and 4 weeks
Mean change in medial temporal-Hippocampal Connectivity
Mean change in
Measured: Baseline and 4 weeks
mean change in plasma amyloid-beta composite score
mean change in amyloid-beta levels in plasma
Measured: Baseline and 4 weeks
Mean change in response time on executive function tasks
Computerized executive function task mean response time in milliseconds
Measured: Baseline and 4 weeks
Mean change in accuracy on executive function tasks
Computerized executive function task mean percent accuracy
Measured: Baseline and 4 weeks
Apolipoprotein (ApoE) e4 allele carrier status
presence of the e4 apolipoprotein based on genetic testing
Measured: Baseline
Cognitive status based on neuropsychological adjudication
Cognitive status of healthy control or mild cognitive impairment
Measured: Baseline
Clinical insomnia status
Diagnosis of insomnia based on clinical cutoffs with self-reported sleep questionnaires
Measured: Baseline
Preclinical Alzheimer's cognitive composite score
Mean Change in Performance on the Preclinical Alzheimer's Cognitive Composite
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start3 Jan 2022
- Primary completion30 Jun 2026
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease, Late OnsetStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to one of two intervention groups. The active group will limit their time in bed for 4 weeks by following a consistent sleep schedule with 85% time in bed compared to their baseline time in bed. The control group will not limit their time in bed, but will be asked to maintain their typical sleep schedule consistent with their baseline time in bed.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Kristine Wilckens, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05138848
- Sponsor's protocol ID
- STUDY20110278
- Other IDs
- R01AG068001
- Acronym
- ALPS
- Status last verified
- Dec 2025
- First submitted
- 7 Nov 2021
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will prepare de-identified data sets comprising all of the data collected for this project and make those available to other investigators through NIH data repositories
Publications
Dong YC, Habte RF, Dessa KM, Fletcher ME, Ianni AM, Lopresti BJ, Aizenstein HJ, Cohen AD, Karikari TK, Weinstein AM, Gebara MA, Wallace ML, Buysse DJ, Wilckens KA. The Alzheimer's Pathways Sleep Study (ALPS): an experimental randomized controlled trial to improve cognition and Alzheimer's pathophysiology through slow-wave sleep. Trials. 2026 Feb 19;27(1):237. doi: 10.1186/s13063-026-09505-w.
PubMed 41715219
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Slow-wave Sleep Enhancement in Those at Risk for Alzheimer's Disease: Links With Memory, Excitotoxicity, and Plasma A-beta
- ClinicalTrials.gov ID
- NCT05138848
- Acronym / sponsor ID
- ALPS / STUDY20110278
- Conditions
- Alzheimer Disease, Late Onset, Mild Cognitive Impairment, Sleep, Cognitive Change, Amyloid
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- 30 Jun 2026 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 1 Dec 2021 (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.
Dementia caused by Alzheimer's disease affects approximately 5.6 million adults over age 65, with costs expected to rise from $307 billion to $1.5 trillion over the next 30 years. Behavioral interventions have shown promise for mitigating neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition and deteriorates with advancing age and Alzheimer's disease. Thus, it is a priority to examine whether improving sleep modifies Alzheimer's disease pathophysiology and cognitive function. Extant research suggests that deeper, more consolidated sleep is positively associated with memory and executive functions and networks that underlie these processes. Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus during sleep may help to preserve the long-range connections that support memory and cognitive function. In pre-clinical Alzheimer's disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown to leave neurons vulnerable to further amyloid deposition. Synaptic downscaling through SWA may mitigate the progression of Alzheimer's disease through these pathways. The proposed study will behaviorally increase sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on amyloid deposition and multiple factors associated with Alzheimer's disease risk. This study will examine whether behaviorally enhanced SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal connectivity, plasma amyloid levels, and cognitive function. This research addresses whether a simple, feasible, and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity, Alzheimer's pathophysiology, and cognitive performance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to one of two intervention groups. The active group will limit their time in bed for 4 weeks by following a consistent sleep schedule with 85% time in bed compared to their baseline time in bed. The control group will not limit their time in bed, but will be asked to maintain their typical sleep schedule consistent with their baseline time in bed.
| Arm | Type | Receives |
|---|---|---|
| Time in Bed Restriction | Experimental | Behavioral: Time in Bed Restriction, Behavioral: Sleep ScheduleTime in Bed (TIB) restriction of 85% of habitual TIB. |
| Control | Active comparator | Behavioral: Sleep ScheduleParticipants will follow their typical sleep schedule consistent with measured average sleep and wake times. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Age 65-85.
- Self-report mean sleep efficiency (the time in bed spent asleep within the time of lights out to final awakening) < 90% based on diary and actigraphy estimates and wake time after sleep onset > 20 minutes based on diary and actigraphy estimates.
- Self-reported normal or corrected-to-normal visual and auditory acuity.
Key exclusion criteria (17 listed)
- Shift work involving night shift or regular work within the hours of 12am and 6am.
- Presence of a chronic condition that significantly affects sleep.
- Severe psychiatric condition including major depressive disorder, panic disorder, substance use disorders, and alcohol abuse/dependence within the past 6 months, or a lifetime history of a psychotic disorder or bipolar I disorder, based on initial online/phone self-report diagnoses, and subsequently based on a structured psychiatric interview.
- Current use of medications affecting sleep such as antidepressants, antipsychotic medications, anticonvulsants, and steroids.
- Current use of sedating drugs used at bedtime.
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 |
|---|---|---|
| Time in Bed RestrictionParticipants will undergo a 4-week sleep intervention that includes specified in- and out-of-bed times as well as a restriction to their habitual time in bed (average sleep opportunity including naps). This will be truncated equally at the beginning and end of the night. | Behavioural | Time in Bed Restriction |
| Sleep ScheduleParticipants will maintain their typical sleep schedule for 4-weeks. | Behavioural | Control, Time in Bed Restriction |
Primary outcome
Mean change in slow-oscillation activity assessed with electroencephalography
Time frame: Baseline and 4 weeks
Slow oscillation electroencephalographic power (0.5-1 Hz) during non-rapid eye movement sleep
Mean change in Hippocampal Activation
Time frame: Baseline and 4 weeks
Change in mean percent signal change of the hippocampus during memory encoding assessed with functional magnetic resonance imaging
Change in mean Plasma amyloid-beta 1-42
Time frame: Baseline and 4 weeks
Change in mean amyloid-beta detected in the plasma in the morning
Overnight memory retention on the AB paired associate task
Time frame: Baseline and 4 weeks
Mean change in percent correct memory
13 secondary outcomes
Mean change in delta activity during sleep
Time frame: Baseline and 4 weeks
Amyloid positivity status
Time frame: Baseline
Mean change in Sleep Efficiency
Time frame: Baseline and 4 weeks
Mean percent signal change in medial prefrontal activation
Time frame: Baseline and 4 weeks
Medial prefrontal-Hippocampal Connectivity
Time frame: Baseline and 4 weeks
Mean change in medial temporal-Hippocampal Connectivity
Time frame: Baseline and 4 weeks
mean change in plasma amyloid-beta composite score
Time frame: Baseline and 4 weeks
Mean change in response time on executive function tasks
Time frame: Baseline and 4 weeks
Mean change in accuracy on executive function tasks
Time frame: Baseline and 4 weeks
Apolipoprotein (ApoE) e4 allele carrier status
Time frame: Baseline
Cognitive status based on neuropsychological adjudication
Time frame: Baseline
Clinical insomnia status
Time frame: Baseline
Preclinical Alzheimer's cognitive composite score
Time frame: 4 weeks
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 6 Jul 2026.
- Derived from this study: PubMed 41715219Dong YC, Habte RF, Dessa KM, Fletcher ME, Ianni AM, Lopresti BJ, Aizenstein HJ, Cohen AD, Karikari TK, Weinstein AM, Gebara MA, Wallace ML, Buysse DJ, Wilckens KA. The Alzheimer's Pathways Sleep Study (ALPS): an experimental randomized controlled trial to improve cognition and Alzheimer's pathophysiology through slow-wave sleep. Trials. 2026 Feb 19;27(1):237. doi: 10.1186/s13063-026-09505-w.
- Individual participant dataSharing planned: Yes. The investigators will prepare de-identified data sets comprising all of the data collected for this project and make those available to other investigators through NIH data repositories
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Time in Bed Restriction and Sleep Schedule in people with Alzheimer Disease, Late Onset and Mild Cognitive Impairment, run by University of Pittsburgh at 1 site 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 3 inclusion and 17 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 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 in slow-oscillation activity assessed with electroencephalography (time frame: Baseline and 4 weeks). 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?
On the ClinicalTrials.gov record for NCT05138848, which also lists 1 linked publication.
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 6 Jul 2026.