Semaglutide for Early Alzheimer's Disease

(EVOKE Plus Trial)

Not currently recruiting at 978 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Alzheimer's treatments

Disqualifiers: Parkinson's, Schizophrenia, Bipolar, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether semaglutide, a medication, can help individuals with early Alzheimer's disease by slowing or improving memory and thinking problems. Participants will receive either semaglutide or a placebo (a harmless pill with no active medicine) and will be monitored for about three years. The trial seeks individuals with mild memory or thinking issues due to Alzheimer's, which affect daily activities like personal care or hobbies. Participants need a study partner to accompany them to clinic visits and phone calls. Various tests, including blood samples and scans, will help researchers evaluate the treatment's effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

If you are taking an approved Alzheimer's treatment, you can continue as long as your dose has been stable for at least 3 months before the study and doesn't change during the study unless necessary.

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

Research has shown that semaglutide, a drug typically used for type 2 diabetes, might help with early Alzheimer's disease. Studies suggest it may reduce the risk of an initial Alzheimer's diagnosis. Semaglutide is generally safe, as it is already approved for diabetes and weight loss. Some individuals might experience mild side effects like nausea or diarrhea, but these often improve over time. This trial will further evaluate its safety and effectiveness for Alzheimer's. ^{1 2 3 4 5}

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

Researchers are excited about semaglutide for early Alzheimer's disease because it offers a fresh approach compared to current treatments like cholinesterase inhibitors and NMDA receptor antagonists. Unlike these standard options, semaglutide, originally a diabetes medication, works by mimicking the hormone GLP-1, potentially reducing inflammation and improving brain function. This unique mechanism could slow the progression of Alzheimer's rather than just alleviating symptoms, providing hope for a more effective treatment strategy.

What evidence suggests that semaglutide might be an effective treatment for early Alzheimer's disease?

Research has shown that semaglutide, initially used for type 2 diabetes, might also aid in treating Alzheimer's disease. Studies have found that semaglutide can reduce the risk of a first-time Alzheimer's diagnosis by 40% to 70% in people with diabetes, compared to other diabetes drugs. This suggests semaglutide could benefit Alzheimer's patients, possibly by influencing certain disease-related processes. Additionally, drugs like semaglutide, part of the GLP-1 group, have been linked to slowing Alzheimer's progression. These findings are promising and suggest that semaglutide, which participants in this trial may receive, might effectively treat early Alzheimer's disease. ^{1 3 4 6 7}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for people aged 55-85 with early Alzheimer's, confirmed by specific tests. They must have certain cognitive scores and stable treatment if they're already on Alzheimer's medication. Participants need a study partner and can't join if pregnant or planning pregnancy during the trial.

Inclusion Criteria

I am between 55 and 85 years old.

My Alzheimer's medication dose has been stable for 3 months.

I have mild dementia, with some difficulty in daily activities.

Exclusion Criteria

You have specific signs of stroke in a brain scan.

I do not have an active severe mental health condition.

I do not have a major neurological disorder besides mild Alzheimer's or MCI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or placebo for the duration of the study

104 weeks

17 clinic visits, 1 phone call

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants continue to be monitored for changes in cognitive scores and adverse events

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo (semaglutide)
• Semaglutide

Trial Overview

The EVOKE Plus study is testing Semaglutide against a placebo to see if it helps with early Alzheimer's disease symptoms. Over roughly 3 years, participants will visit clinics for tests and scans, including blood samples at some visits.

How Is the Trial Designed?

Group I: Oral semaglutide Experimental Treatment 1 Intervention

Participants are given oral semaglutide once daily

Group II: Placebo (semaglutide) Placebo Group 1 Intervention

Participants are given oral placebo once daily

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In a 56-week study involving 1231 participants with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.3% and 1.6% for the 0.5 mg and 1.0 mg doses, respectively, compared to a 0.5% reduction with sitagliptin, demonstrating superior efficacy in glycaemic control.

Semaglutide also led to greater weight loss, with reductions of 4.3 kg and 6.1 kg for the two doses, compared to 1.9 kg with sitagliptin, while maintaining a similar safety profile, primarily with gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Ahrén, B., Masmiquel, L., Kumar, H., et al.[2022]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Semaglutide has shown potential protective effects against Alzheimer's disease by enhancing autophagy and inhibiting apoptosis in SH-SY5Y cells treated with Aβ25-35, a model for Alzheimer's.

The study found that semaglutide increased levels of autophagy-related proteins (like LC3II and Beclin-1) and decreased apoptosis-related proteins (like Bax), suggesting a mechanism through which it may help protect against neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. Chang, YF., Zhang, D., Hu, WM., et al.[2021]

In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.

Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. Janić, M., Jovanović, M., Janež, A., et al.[2023]

Semaglutide significantly reduced HbA1c levels in both non-elderly (1.2%-1.5%) and elderly (1.3%-1.5%) patients with type 2 diabetes compared to comparators, demonstrating its efficacy across age groups.

The safety profile of semaglutide was comparable in both age groups, with no increased risk of severe hypoglycemia, making it a suitable treatment option for elderly patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Warren, M., Chaykin, L., Trachtenbarg, D., et al.[2022]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

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GLP-1s have gained attention for a surprising new possibility: helping to treat Alzheimer's. Learn about EVOKE/EVOKE+ clinical trials and ...

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Weight Loss Drugs May Protect Against Alzheimer's

Popular weight loss drugs like Ozempic and Wegovy may cut the risk of Alzheimer's disease and other forms of dementia, a large new analysis found.

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Glucagon-like peptide-1 (GLP-1) drugs, like Ozempic® and Wegovy®, may slow Alzheimer's progression. · They target multiple disease pathways at ...

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Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications.

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evoke and evoke+: design of two large-scale, double-blind ...

Treatment with GLP-1RAs significantly decreases risk of dementia, and in preclinical studies, the GLP-1RA semaglutide has shown positive effects ...