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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
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.
Matched oral Placebo to be taken once daily.
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.
Time frame: Adverse events monitoring: Baseline; Weeks 4, 8, 26, 39, 52
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.
Time frame: [18F] SynVesT-1 PET will be conducted at baseline and Week 52 (end of treatment).
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