A national Alzheimer’s disease trial has begun recruiting participants at NHS sites in Cambridgeshire and Peterborough and Surrey and Borders, testing metformin and atomoxetine within a shared, flexible study. The AD-SMART trial is designed to assess several treatments at once and to stop testing a treatment arm if interim results indicate it is not showing benefit. Its opening marks the start of an investigation, not evidence that either medicine works against Alzheimer’s disease.
Two existing medicines enter testing
The first medicines being studied are metformin, commonly used to treat type 2 diabetes, and atomoxetine, used for attention deficit hyperactivity disorder. Both are being repurposed for research into Alzheimer’s. Researchers will examine whether either can help with symptoms including memory and thinking difficulties, while also assessing quality of life and daily functioning.
Participants are allocated to treatment groups, with results compared against a shared placebo group as well as the medicines being tested. A placebo is a dummy treatment. The platform design allows researchers to evaluate multiple arms within one trial rather than establishing a separate study for every candidate medicine. The initial programme is intended to recruit 1,200 people across the UK, with more than 30 sites planned overall.
Trial arms can change as evidence develops
AD-SMART uses a multi-arm, multi-stage adaptive design. Researchers plan to review results at stages during the study. A treatment arm that is not showing sufficient promise can be discontinued, while other possible treatments may be added. This is intended to make testing more efficient and limit the number of participants assigned to treatments that are not performing well.
The initial two medicines are expected to be evaluated through 2030. Additional treatment arms may be introduced during that period, so the trial is designed to continue adapting as candidates emerge. Researchers say comparing several treatments with one shared control can reduce the time needed to evaluate them compared with running separate conventional trials. That is a potential efficiency of the design, not a prediction that a particular treatment will succeed.
Recruitment has started, with more sites expected
The first participants have been recruited through Cambridgeshire and Peterborough NHS Foundation Trust and Surrey and Borders Partnership NHS Foundation Trust. Other sites are open in West London, Edinburgh and Southampton, and further NHS locations are expected to come online. The sites in Cambridgeshire and Surrey therefore form part of a UK-wide programme rather than a trial limited to those areas.
People with a confirmed Alzheimer’s diagnosis who are interested in taking part can register their interest with the study team. Eligibility and enrolment are assessed by researchers; registering interest does not itself mean that someone can join the trial. Participants undergo assessments during follow-up, including measures of thinking and everyday activities, so that researchers can compare changes over time.
Effectiveness remains to be established
Metformin and atomoxetine are established medicines for other conditions, but that does not establish that they are effective treatments for Alzheimer’s. The purpose of AD-SMART is to test whether they provide meaningful benefit in this new setting and to monitor safety. The study’s findings will be needed before conclusions can be drawn about any effect on Alzheimer’s symptoms or progression.
The trial is led by the UK Dementia Research Institute and Alzheimer’s Research UK, with delivery involving university and clinical research partners. Its adaptive structure could help researchers assess multiple candidates in a more coordinated way. For patients and families, however, the immediate development is that recruitment and testing have started; no benefit from either of the first two medicines has yet been demonstrated by this launch announcement.
