Suvorexant for Alzheimer's Disease

(SToP-AD Trial)

Recruiting at 1 trial location

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?

The purpose of this study is to determine if treatment with the sleep aid suvorexant can decrease the rate of amyloid-β (Aβ) accumulation in the brain.

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.

How does the drug Suvorexant differ from other Alzheimer's treatments?

Suvorexant is unique because it is primarily used as a sleep aid, working by blocking orexin receptors in the brain, which are involved in wakefulness. This mechanism is different from other Alzheimer's treatments that often target amyloid plaques or neurotransmitter systems. ^{1 2 3 4 5}

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 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 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]

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 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]

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. Poland 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). [2021]

2. United States 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. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Cortical florbetapir-PET amyloid load in prodromal Alzheimer's disease patients. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Association of the top 20 Alzheimer's disease risk genes with [18F]flortaucipir PET. [2023]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Alzhemed: a potential treatment for Alzheimer's disease. [2019]