Alzheimer DiseasePhase 2NCT07200622
Oral Semaglutide in Patients With Alzheimer's Disease
A Phase 2 study testing Semaglutide (Rybelsus®) in people with Alzheimer Disease, run by Imperial College London.
Trial summary
Alzheimer's disease (AD) is a progressive neurodegenerative disease and a major global healthcare burden. Currently, the disease is only treated symptomatically and an effective disease-modifying therapy (DMT) that may slow the disease progression, and prevent cognitive and functional deterioration, is yet to emerge. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Semaglutide (Rybelsus®)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 25 Sep 2025to 31 Dec 2028
- Phase
- Phase 2
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving and capacity to give informed consent.
- An individual who can act as a reliable study partner with regular contact
- Diagnosis of Alzheimer's disease according to the revised NIA-AA criteria
- Age from 50 years
- Mini-Mental State Examination (MMSE) score of ≥18; likely complete all the assessments
- Rosen Modified Hachinski Ischemic score ≤4
Show all 9Show fewer
- On stable medication for 2 months before the screening visit; on or off cholinesterase inhibitors
- Fluency in English and evidence of adequate premorbid intellectual functioning
- Likely to be able to participate in all scheduled evaluations and complete all required tests
Who cannot join
- Any contraindications to the use of oral semaglutide
- Significant neurological disease other than AD that may affect cognition
- MRI/CT showing unambiguous aetiological evidence of cerebrovascular disease with regard to their dementia or vascular dementia fulfilling NINCDSAIREN criteria
- Current presence of a clinically significant major psychiatric disorder
- Current clinically significant systemic illness that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study
- Myocardial infarction within the last 1 year
Show all 14Show fewer
- Other clinically significant abnormality on physical, neurological or laboratory examination that could compromise the study or be detrimental to the subject
- History of alcohol or drug dependence within the last 2 years
- Current use of narcotic medications which could affect cognition. Subjects on anticoagulants will be allowed, but will not have an arterial line inserted
- Women of childbearing potential. Women who could become pregnant will be required to use adequate contraception throughout the trial. Please see appendix A for more information. All women of childbearing potential will take a pregnancy test before the PET scan.
- Any contraindications to MRI scanning
- Any historical evidence of pancreatitis or gallstones as proven by ultrasound or medical admission.
- History of medullary thyroid cancer
- Patients diagnosed with T2DM who are unwilling to change their treatment to semaglutide.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Evaluating the Effects of GLP-1 Analogue, Oral Semaglutide, in Patients With Alzheimer's Disease
Alzheimer's disease (AD) is a progressive neurodegenerative disease and a major global healthcare burden. Currently, the disease is only treated symptomatically and an effective disease-modifying therapy (DMT) that may slow the disease progression, and prevent cognitive and functional deterioration, is yet to emerge. Glucagon-like peptide-1 (GLP-1) analogues are being studied to treat neurodegenerative diseases, due to evidence of their neuroprotective effects in mouse models of AD. This study investigates Semaglutide, a modified human GLP-1RA in Alzheimer's disease to understand the mechanism of the disease. The primary objective of this study is to evaluate the safety and tolerability of oral semaglutide in individuals with mild AD. Moreover, the secondary objective of the study is to evaluate the change in synaptic density using PET before and after treatment with semaglutide.
- Conditions
- Alzheimer Disease
- Being tested
- Semaglutide (Rybelsus®), Placebo
- Keywords
- GLP-1 Analogues, Semaglutide, Alzheimers
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide (Rybelsus®)Drug
All subjects will receive oral semaglutide once daily (4-weekly dose escalation from 3 mg to 7 mg and finally 14 mg). This dose escalation schedule is specified in the IMP (Rybelsus) SmPC.
PlaceboDrug
Matched oral Placebo to be taken once daily.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide (Rybelsus) | Experimental | Not described Receives: Drug: Semaglutide (Rybelsus®) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of oral semaglutide in an AD population.
To assess the safety and tolerability of (1-year) Semaglutide treatment in patients with AD using composite outcome measure of the adverse events evaluated from the safety assessments. This will be assessed by the number of participants using a composite measure generated from abnormal vital signs, abnormal 12-lead ECG readings, abnormal laboratory (blood) tests, abnormalities found in MRI scans, abnormal physical exam findings, and abnormal neurological/psychiatric evaluation.
Measured: Adverse events monitoring: Baseline; Weeks 4, 8, 26, 39, 52
Secondary outcomes (1)
To evaluate the change in synaptic density using [18F] SynVesT-1 before and after treatment.
Synaptic density will be assessed, using [18F] SynVesT-1, at baseline and after 1-year of treatment with Semaglutide.
Measured: [18F] SynVesT-1 PET will be conducted at baseline and Week 52 (end of treatment).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2025
- Study start25 Sep 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A 12-month, multicentre, randomised, double-blind, placebocontrolled study in patients with mild to moderate Alzheimer's dementia. Subjects will be randomised on a 1:1 ratio to receive oral semaglutide or matching placebo. Participants will be maintained at the highest well-tolerated daily dose.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07200622
- Sponsor's protocol ID
- 21HH7080
- Status last verified
- Sep 2025
- First submitted
- 18 Sep 2025
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided