Sleep Schedule Restriction for Alzheimer's Disease

(ALPS Trial)

Overseen By Brian Lopresti, M.C.

Age: 65+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pittsburgh

Must not be taking: Antidepressants, Antipsychotics, Anticonvulsants, Steroids

Disqualifiers: Severe psychiatric conditions, CNS diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

116 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a sleep intervention can improve brain health for those at risk of Alzheimer's disease. Participants will either maintain their usual sleep habits or follow a program called Time in Bed Restriction, which limits time in bed to enhance sleep quality. Researchers aim to determine if better sleep can reduce harmful brain activity and improve memory. Individuals who may be suitable for this trial often experience difficulty sleeping through the night and have concerns about Alzheimer's disease. As an Early Phase 1 trial, this research focuses on understanding how the sleep intervention works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

Yes, if you are currently using medications that affect sleep, such as antidepressants, antipsychotics, anticonvulsants, steroids, or sedating drugs used at bedtime, you will need to stop taking them to participate in this trial.

What prior data suggests that this sleep schedule restriction is safe for Alzheimer's patients?

Studies have shown that spending less time in bed can enhance sleep efficiency and improve deep sleep, which is linked to better memory and thinking skills. Researchers have safely used this method in older adults who struggle with staying asleep, resulting in better quality and deeper sleep.

Although daytime sleepiness might occur, this approach is generally considered as safe as cognitive behavioral therapy for insomnia (CBT-I). It is usually safe and could improve sleep without major side effects. However, since this is an early phase study, researchers are still learning about its full safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Time in Bed Restriction for Alzheimer's Disease because it's exploring a non-drug approach to potentially improve sleep and cognitive function. Unlike standard treatments that often involve medications targeting amyloid plaques or neurotransmitter imbalances, this method focuses on adjusting sleep patterns by restricting time in bed to 85% of habitual time. This could offer a more natural and less invasive option, potentially reducing reliance on pharmaceuticals and their associated side effects.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research has shown that adjusting sleep schedules might help people with Alzheimer's disease by improving sleep quality. In this trial, participants in the "Time in Bed Restriction" arm will spend less time in bed. Studies suggest this can make sleep more efficient and increase deep sleep, known as slow-wave activity (SWA). SWA is crucial because it helps the brain refresh connections, particularly in memory-related areas. Better SWA may reduce overactivity in brain regions affected by Alzheimer's, possibly slowing the disease's progression. Early findings indicate that improving sleep in this manner could enhance memory and thinking skills. Meanwhile, participants in the "Control" arm will maintain their typical sleep schedule. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for older adults aged 65-85 with sleep difficulties but without severe psychiatric conditions, heavy alcohol or caffeine consumption, CNS diseases like Alzheimer's, or certain medications that affect sleep. Participants should have normal vision and hearing (with aids if necessary), a tendency to wake up often at night, and not be involved in shift work.

Inclusion Criteria

You can see and hear normally or with corrective lenses or aids.

You have trouble sleeping, as shown by your sleep diary and activity tracker, with a low sleep efficiency and long periods of being awake after falling asleep.

I am between 65 and 85 years old.

Exclusion Criteria

You have a score higher than 10 on the Epworth sleepiness test.

You drink more than 14 alcoholic drinks per week or more than 6 drinks at one time.

You have a serious mental health condition like severe depression, panic disorder, substance abuse, or bipolar disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a time-in-bed restriction intervention to increase sleep efficiency and slow-wave activity

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for changes in cognitive function and sleep patterns after the intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sleep Schedule
• Time in Bed Restriction

Trial Overview The study tests whether restricting the time spent in bed can improve deep sleep and cognitive function in older adults. It aims to see if this intervention can reduce brain overactivity related to Alzheimer's disease risk by enhancing slow-wave activity during sleep.

How Is the Trial Designed?

Group I: Time in Bed Restriction Experimental Treatment 2 Interventions

Time in Bed (TIB) restriction of 85% of habitual TIB.

Group II: Control Active Control 1 Intervention

Participants will follow their typical sleep schedule consistent with measured average sleep and wake times.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 46 institutionalized patients with severe Alzheimer's disease, morning bright light therapy significantly improved rest-activity rhythm in those with the most severe disruptions, indicating its potential as a targeted intervention.

However, the overall effectiveness of bright light therapy on sleep quality and rest-activity measures was limited, suggesting that it may not benefit all patients equally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of morning bright light treatment for rest-activity disruption in institutionalized patients with severe Alzheimer's disease. Dowling, GA., Hubbard, EM., Mastick, J., et al.[2019]

Accumulation of amyloid-β (Aβ) in the brain is a key factor in the development of Alzheimer's disease (AD), and sleep deprivation can increase Aβ levels, suggesting a link between sleep patterns and AD progression.

Individuals with early signs of Aβ deposition often experience sleep abnormalities, indicating that sleep disturbances may be an early indicator of Alzheimer's disease and highlighting the potential for sleep management in diagnosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep and Alzheimer disease pathology--a bidirectional relationship. Ju, YE., Lucey, BP., Holtzman, DM.[2022]

Many patients with Alzheimer's disease experience significant sleep disruptions, which may not only be a symptom of the disease but could also contribute to its progression.

Research suggests that addressing these sleep disturbances could potentially target underlying mechanisms of Alzheimer's, indicating that effective sleep interventions might help modify the disease course, although further large-scale studies are needed to confirm this.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep and its regulation: An emerging pathogenic and treatment frontier in Alzheimer's disease. Kent, BA., Feldman, HH., Nygaard, HB.[2022]

Accumulation of amyloid-β (Aβ) plaques in Alzheimer's disease is linked to increased sleep-wake disturbances, suggesting that Aβ pathology may disrupt normal sleep patterns.

Chronic sleep deprivation can worsen Alzheimer's disease by increasing amyloid plaque deposition, while improving sleep may help reduce plaque levels, indicating a potential therapeutic target for managing sleep disorders in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sleep-wake cycle and Alzheimer's disease: what do we know? Lim, MM., Gerstner, JR., Holtzman, DM.[2018]

In a study of 59 cognitively unimpaired older adults, traditional sleep metrics did not show differences between those with and without β-amyloid (Aβ) positivity, suggesting these measures may not be reliable indicators of preclinical Alzheimer's disease.

However, using a novel analysis method, researchers found that Aβ-positive participants exhibited distinct patterns of activity, including lower late-night activity and higher early morning activity, indicating potential alterations in rest/activity rhythms that could serve as markers for preclinical Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies. Spira, AP., Zipunnikov, V., Raman, R., et al.[2023]

The article proposes new standards for identifying and naming sleep/wake cycle disturbances in Alzheimer's disease (AD) to improve research and treatment development, highlighting the significant impact these disturbances have on patients and caregivers.

The FDA has recognized the need for a comprehensive diagnostic system for behavioral problems in dementia, indicating that better-defined criteria could facilitate pharmacological research and lead to effective treatments for sleep disturbances in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of diagnostic criteria for defining sleep disturbance in Alzheimer's disease. Yesavage, JA., Friedman, L., Ancoli-Israel, S., et al.[2017]

In a study involving 132 participants with Alzheimer's disease, interventions like walking, light exposure, and a combination of both showed significant improvements in total wake time compared to a control group, indicating potential benefits for sleep quality.

Better adherence to the walking and light exposure recommendations (at least 4 days a week) was linked to significantly less total wake time and improved sleep efficiency, highlighting the importance of consistent participation in these activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing walking and bright light exposure to improve sleep in community-dwelling persons with Alzheimer's disease: results of a randomized, controlled trial. McCurry, SM., Pike, KC., Vitiello, MV., et al.[2022]

In patients with moderate to severe Alzheimer's disease (AD), cerebrospinal fluid levels of orexin were significantly higher compared to controls, indicating a potential dysregulation of the orexinergic system as the disease progresses.

Higher orexin levels were correlated with greater sleep disturbances and cognitive decline, suggesting that the changes in orexin levels may contribute to the sleep-wake cycle disruptions commonly seen in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. Liguori, C., Romigi, A., Nuccetelli, M., et al.[2015]

In a study involving 10 Alzheimer's patients with severe sundowning, exposure to evening bright light for 2 hours a day significantly improved sleep-wake patterns in 8 out of 10 patients.

The treatment not only reduced nighttime activity but also increased the stability of the circadian rhythm, suggesting that bright light may help regulate sleep disturbances through a chronobiological mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease. Satlin, A., Volicer, L., Ross, V., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05138848

Time-in-bed Restriction in Older Adults With Sleep ... Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/312355

Time-in-bed Restriction in Older Adults With Sleep ... Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity ( ...

3. withpower.com withpower.com/trial/phase-late-onset-disorders-11-2021-35ba1

Sleep Schedule Restriction for Alzheimer's Disease Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest ...

4. frontiersin.org frontiersin.org/journals/sleep/articles/10.3389/frsle.2023.1265006/full

A pilot time-in-bed restriction intervention behaviorally ... A TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8073746/

Sleep-Based Interventions in Alzheimer's Disease: Promising ... Results showed that EDS was significantly associated with a 30% increased risk of developing cognitive decline. The number of insomnia ...

6. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.8164

Risk of excessive sleepiness in sleep restriction therapy and ... SRT appears to have a comparable risk profile for excessive sleepiness as CBT-I, and thus may be considered a safe alternative to CBT-I.