UK Launches First Platform Trial to Test Multiple Repurposed Alzheimer's Drugs at Once

AD-SMART, a national platform trial coordinated by the UK Dementia Research Institute at Imperial College London and Alzheimer's Research UK, has enrolled its first participants, according to an Imperial College London announcement and the trial's registration with the ISRCTN registry. The trial will test a repurposed attention deficit hyperactivity disorder drug and a repurposed type 2 diabetes drug against one shared placebo group. The first participants were recruited at Cambridgeshire and Peterborough NHS Foundation Trust and Surrey and Borders Partnership NHS Foundation Trust, with sites also open at Imperial College Healthcare NHS Trust, in Edinburgh and in Southampton, Imperial said.

AD-SMART uses a multi-arm, multi-stage design borrowed from cancer research: instead of one drug tested against one placebo group, separate groups of participants are randomised to different drugs, and all are compared against a single shared placebo arm layered onto standard care. According to the ISRCTN registration, participants in this first stage are allocated 1:1:1 to standard care plus placebo, standard care plus atomoxetine, or standard care plus metformin. Built-in checks at set stages let the trial drop a drug that shows no benefit and add a new one without restarting, a design its organisers say could more than halve the time typically needed to test a single Alzheimer's treatment, per Imperial. The trial aims to recruit 1,200 participants with symptomatic Alzheimer's disease, with up to 20 NHS sites expected to open over the next 12 to 18 months and more than 30 planned in total, Imperial and the NIHR reported.

The launch marks the start of recruitment, not a result. Atomoxetine and metformin were chosen by an international expert panel working with people with lived experience of Alzheimer's, based on early-stage human studies and laboratory research rather than evidence that either drug treats Alzheimer's disease. Chief investigator Professor Paresh Malhotra said both drugs are thought to act on inflammation pathways linked to neurodegeneration, a mechanism the trial itself has not yet tested, according to remarks reported by Medscape from a Science Media Centre briefing. The ISRCTN registration lists the trial's main objective as measuring change in cognitive function and activities of daily living over 18 months of treatment; evaluation of these first two drugs is not expected to finish until around 2030, with the overall trial registered to run to March 2031.