Suvorexant for Alzheimer's Disease

(SToP-AD Trial)

Recruiting at 2 trial locations

Overseen By Chloe Meehan, MA

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Sedatives, Suvorexant interactors

Disqualifiers: Stroke, Chronic kidney disease, HIV/AIDS, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the sleep aid suvorexant can slow the build-up of amyloid-β, a protein linked to Alzheimer's, in the brain. Participants will take either suvorexant or a placebo (a harmless pill with no active medicine) daily for two years. The trial targets individuals aged 65 or older who have trouble sleeping but do not have conditions like sleep apnea or other major health issues. Those with poor sleep who meet these criteria might find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications, especially if they interact with suvorexant or are sedating. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that suvorexant is likely to be safe for humans?

Research shows that suvorexant is generally safe for people with Alzheimer's disease. Studies have found that it improves sleep without causing many serious side effects. Most people tolerate it well for up to 12 months, indicating that they can use it without problems. However, information on its safety for longer use is not available.

The FDA has already approved suvorexant for treating insomnia, indicating its safety for many people. This trial examines its effect on brain changes in Alzheimer's, making safety a crucial consideration. Based on current evidence, suvorexant appears to be a safe option for improving sleep in those with Alzheimer's. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Suvorexant is unique because it targets the orexin system, which is involved in regulating sleep and wakefulness. Unlike standard Alzheimer's treatments, which often focus on memory and cognition, suvorexant specifically aims to improve sleep quality, a common issue in Alzheimer's patients. Researchers are excited about this treatment because improving sleep may not only enhance patients' overall well-being but could also potentially slow the progression of Alzheimer's symptoms by allowing the brain more time to rest and repair.

What evidence suggests that suvorexant might be an effective treatment for Alzheimer's?

Research has shown that suvorexant can help people with Alzheimer's disease sleep better. In studies, patients who took suvorexant slept longer, as confirmed by overnight sleep tests. This medication is already approved for treating insomnia, a condition where people have trouble sleeping. In this trial, participants in the poor sleep treatment group will receive suvorexant to assess its impact on sleep and Alzheimer's progression. For Alzheimer's patients, better sleep might help reduce the buildup of a protein called amyloid-β (Aβ), which is linked to the progression of Alzheimer's. These findings suggest that suvorexant could potentially slow Alzheimer's disease by improving sleep. ^{1 2 3 5 6}

Who Is on the Research Team?

Brendan Lucey, MD

Principal Investigator

Washington Univeristy School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals aged 65 or older with early signs of Alzheimer's, as indicated by specific brain scan results and cognitive assessments. They must be able to consent and follow study procedures. Excluded are those with certain sleep disorders, severe health conditions, recent substance abuse, high alcohol intake, obesity (BMI >35), or on conflicting medications.

Inclusion Criteria

I am 65 or older and can give my consent.

I understand the study and can follow its procedures.

Your PET scan shows a certain level of brain activity between a specific range.

Exclusion Criteria

You have been drinking alcohol regularly, at least 3 days a week for the past 6 months, and typically have more than 2 drinks within 3 hours of going to bed. If you agree to drink less during the study, this rule may not apply to you.

I use a PAP machine for my sleep disorder or my AHI score is over 15.

My sleep efficiency is 85% or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive suvorexant 20mg or placebo daily for two years to assess its effect on amyloid-β accumulation

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Suvorexant

Trial Overview The trial tests if suvorexant, a sleep aid medication at a dose of 20 mg, can slow down the buildup of amyloid-β in the brain compared to a placebo. Amyloid-β accumulation is associated with Alzheimer's disease progression.

How Is the Trial Designed?

Group I: Poor sleep treatment group Experimental Treatment 1 Intervention

100 participants will be randomized to take suvorexant 20mg daily at h.s. for two years

Group II: Poor sleep control grop Placebo Group 1 Intervention

100 participants will be randomized to take placebo daily at h.s. for two years.

Suvorexant is already approved in United States, Japan for the following indications:

Approved in United States as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Approved in Japan as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Good Ventures Foundation

Collaborator

Trials

1

Recruited

200+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Good Ventures

Collaborator

Trials

1

Recruited

200+

Published Research Related to This Trial

In a study of 22 patients at the prodromal stage of Alzheimer's disease and 17 matched controls, AV-45 showed significantly higher cortical uptake in patients, indicating increased amyloid load associated with early Alzheimer's.

The research found specific correlations between higher levels of cortical amyloid and cognitive decline in memory performance, suggesting that AV-45 can be a useful tool for assessing early cognitive impairment in Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical florbetapir-PET amyloid load in prodromal Alzheimer's disease patients. Saint-Aubert, L., Barbeau, EJ., Péran, P., et al.[2021]

In a study involving 1,052 patients with mild-to-moderate Alzheimer's disease, tramiprosate showed a significant reduction in hippocampus volume loss compared to placebo, suggesting potential disease-modifying effects.

While the primary analyses did not demonstrate a significant cognitive improvement, post-hoc analyses indicated a trend towards cognitive benefits, highlighting the need for further investigation into tramiprosate's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tramiprosate in mild-to-moderate Alzheimer's disease - a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Aisen, PS., Gauthier, S., Ferris, SH., et al.[2021]

In a study involving 566 participants across different cognitive stages (cognitively normal, mild cognitive impairment, and dementia), the APOE ε4 gene variant was significantly associated with tau deposition in the brain, indicating its role in Alzheimer's disease progression.

Other genetic variants, including ABCA7, CR1, BIN1, and CASS4, were also linked to tau deposition, suggesting that these genes may influence tau metabolism and contribute to Alzheimer's disease pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of the top 20 Alzheimer's disease risk genes with [18F]flortaucipir PET. Stage, E., Risacher, SL., Lane, KA., et al.[2023]

In the ongoing phase 1b PRIME study involving patients with prodromal or mild Alzheimer's disease, aducanumab treatment led to significant reductions in amyloid PET SUVR, indicating a decrease in amyloid plaque burden over time and with higher doses.

The choice of reference regions for calculating SUVR significantly influenced effect sizes, with subcortical white matter and the pons yielding the largest effect sizes, while using the anterior cingulate cortex as a target ROI provided better results than a composite cortex approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Reference and Target Region Selection on Amyloid PET SUV Ratios in the Phase 1b PRIME Study of Aducanumab. Chiao, P., Bedell, BJ., Avants, B., et al.[2019]

Alzhemed (tramiprosate) is a well-tolerated treatment for mild-to-moderate Alzheimer's disease that effectively reduces levels of the neurotoxic amyloid-beta peptide in the cerebrospinal fluid after 3 months of treatment.

While Alzhemed did not show immediate cognitive improvements after 3 months, long-term follow-up suggested stabilization of cognitive function, particularly in patients with mild Alzheimer's disease, indicating potential benefits over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzhemed: a potential treatment for Alzheimer's disease. Aisen, PS., Gauthier, S., Vellas, B., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02750306

NCT02750306 | Safety and Efficacy of Suvorexant (MK- ... This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7984350/

Polysomnographic assessment of suvorexant in patients ... Interpretation: Suvorexant was effective at increasing total sleep time as assessed by polysomnography in patients with mild‐to‐moderate ...

3. merck.com merck.com/news/mercks-belsomra-suvorexant-c-iv-meets-primary-efficacy-endpoint-in-phase-3-trial-for-the-treatment-of-insomnia-in-people-with-mild-to-moderate-alzheimers-disease-dementia/

Merck's BELSOMRA® (suvorexant) C-IV Meets Primary ... This is the first dedicated Phase 3 polysomnography study of an insomnia medication in people with mild-to-moderate Alzheimer's disease dementia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02750306?term=AREA%5BBasicSearch%5D(mk-4305)&rank=4

Safety and Efficacy of Suvorexant (MK-4305) for the ... This study aims to examine the safety and efficacy of suvorexant ( MK-4305 ) to improve sleep in individuals with Alzheimer's disease (AD).

5. mayo.edu mayo.edu/research/clinical-trials/cls-20265559

A Study of the Safety and Effectiveness of Suvorexant (MK- ... The purpose of this study is to examine the safety and effectiveness of suvorexant (MK-4305) to improve sleep in individuals who have Alzheimer's disease.

6. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Suvorexant-Cognitive-Vitality-For-Researchers.pdf

Suvorexant Safety: Good safety profile for up to 12 months but no data on long-term use of suvorexant. Animal research suggests that orexin is important for systems like ...