Alzheimers disease Nervous System Diseases Alzheimer disease
Conditions
Interventions
Intervention: Semaglutide 3, 7 and 14 mg tablets, titrated to 14 mg once daily, oral
Comparator: Matching placebo, once-daily, oral
The total duration of treatment is 52 weeks for both arms
follow-up is 5 to 6 weeks following treatment completion.
At their randomisation visit, study participants who fulfil all the inclusion criteria and violate none of the exclusion criteria will be as
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
55 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. Participant is willing and able to give informed consent for participation in the trial 2. Male or female, aged 55 years or above 3. Amyloid-positivity as evidenced by PET 4. Fluent English speaker, as assessed by the Investigator 5. In the Investigator’s opinion, is able and willing to comply with all trial requirements 6. Willing to allow his or her General Practitioner (GP), if appropriate, to be notified of participation in the trial 7. Clinical dementia rating (CDR) of 0.5 or below. 8. An informant that is available to the research team for the purposes of CDR scoring
Exclusion criteria
Exclusion criteria: 1. Diagnosis of dementia 2. Treatment with a GLP-1 RA: current or in the past 6 months 3. Women who are pregnant, breastfeeding or of childbearing potential (see Appendix D for definition) 4. People with type 1 diabetes mellitus, secondary diabetes, or maturity-onset diabetes of the young (MODY) 5. People with T2DM who have pre-proliferative or proliferative diabetic retinopathy, or diabetic maculopathy 6. People with T2DM if the cap of 30% of participants with T2DM randomised has been met 7. Poorly controlled T2DM, defined as HbA1c =10% (86 mmol/mol) 8. Evidence of severe renal impairment or an estimated glomerular filtration rate (eGFR) derived from serum creatinine (using the simple CKD-EPI formula) of <30 ml/min/1.73 m² 9. Evidence of hepatic cirrhosis as assessed by medical history 10. A psychiatric condition which in the opinion of the investigator may affect the safety of the participant or the outcomes of the study. 11. Any contraindication for MRI or PET scans, including but not limited to: MR-incompatible pacemakers, pregnancy, aneurysm clip, implanted neural stimulator, implanted cardiac pacemaker or auto-defibrillator, cochlear implant, ocular foreign body, recent carotid stent, CSF shunt, other implanted medical device, e.g., Swan Ganz catheter, insulin pump, as assessed by a standard pre-MRI questionnaire 12. Participant with a life expectancy of fewer than 6 months 13. Currently enrolled in another investigational device or drug study, or less than 30 days between randomisation and ending another investigational device or drug study or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded 14. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in-situ carcinomas of the cervix, or in situ prostate cancer) within 5 years prior to the day of screening 15. Lack of access to a suitable digital technology to allow remote cognitive testing (PC or tablet connected to the internet) 16. Significant eye or hearing impairment that in the opinion of the investigator may affect study procedures 17. People with the low-affinity binding variant of the rs6971 allele of the TSPO gene 18. Known or suspected hypersensitivity to the trial product or related products 19. Poor venous access or other contraindications that would make blood sampling difficult 20. Participant that in the view of the investigator will experience significant distress in the event of a positive amyloid status disclosure. Such individuals will not undergo amyloid screening 21. Diabetic individuals treated with sulphonylureas or insulin where dose adjustment as described in protocol is not possible for whatever reason 22. Individuals with significant radiation exposure in the past year for whom in the opinion of the investigator the additional exposure will result in an unacceptable risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 01/05/2024: The primary endpoint is the annualised change in cortical tau. It is measured at baseline and 52-week visits using PET tau and expressed in standardised uptake value ratio (SUVR). Previous primary outcome measure: Tau cortical standardized uptake value ratio (SUVR) measured using positron emission tomography (PET) at baseline and following treatment at week 52 (visit 7) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 01/05/2024: 1. Cortical neuroinflammatory signal measured using translocator protein (TSPO) PET SUVR at baseline and 52 weeks 2. Plasma biomarkers of neuroinflammation measured by estimating plasma glial fibrillary acidic protein (GFAP) protein levels at screening, baseline, weeks 4, 8, 26, 39 and 52 3. Plasma AD biomarkers: p-tau181 levels and Aß42/40 ratio at screening, baseline, weeks 4, 8, 26, 39 and 52 4. Cognition measured in-clinic with pen and paper cognitive test (Addenbrooke’s Cognitive Assessment [ACE-III]) scores at baseline, weeks 26 and 52 as well as computerised in-clinic cognitive battery (CANTAB) at baseline, weeks 26 and 52. Cognition is also measured remotely through a browser-based cognitive battery (Cognitron) 1 at baseline, weeks 26 and 52 5. Presence of Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs), Serious Adverse Reactions (SARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs). Information on those is collected through interviews at baseline, weeks 4, 8, 26, 39, 52 and follow-up call 6. Neurodegeneration measured by determination of hippocampal volume using structural MRI at baseline and 52 weeks as well as plasma levels of neurofilament light (NFL) measured at screening, baseline, weeks 4, 8, 26, 39 and 52 7. Depression and anxiety scores measured by the Center for Epidemiologic Studies Depression Scale (CES-D) and Health Anxiety Inventory (HAI) scales at baseline and 52 weeks 8. Levels of distress at AD risk disclosure measured through the Impact of Genetic Testing for Alzheimer's disease scale at weeks 26 and 52 9. Quality of life measured by EQ-5D-5L scales at baseline and 52 weeks 10. Level and pattern of physical activity and circadian rhythms measured using wrist-worn actigraphy at baseline and 52 weeks Previous secondary outcome measures: 1. Neuroinflammation measured using Translocator protein (TSPO) PET SUVR, plasma glial fibrillary acidic protein | — |
Countries
England, United Kingdom
Contacts
Public ContactElliot Mann
Outcome results
None listed