The AD-SMART trial will initially test two repurposed medicines. One is metformin, widely used to treat type 2 diabetes. The other is atomoxetine, a drug prescribed for attention deficit hyperactivity disorder, or ADHD. An international expert panel selected these drugs based on early evidence that they may reduce brain inflammation, which scientists believe is one of the drivers of neurodegeneration in Alzheimer’s disease.

Professor Paresh Malhotra, chief investigator of the study and group leader at the UK Dementia Research Institute Centre for Care Research & Technology at Imperial College London, described a central problem in Alzheimer’s research. He noted that for too long progress has followed a pattern of one drug, one trial, one answer, often taking a decade or more for each attempt. AD-SMART is a deliberate effort to break this pattern and accelerate the path to answers for patients and families.

The design of the trial is particularly notable. AD-SMART is a multi-arm, multi-stage platform trial. Instead of testing a single drug against a placebo over many years, it evaluates several treatments at the same time against one shared placebo group. People who join the study have a higher chance of receiving an active treatment compared with many traditional trials, where a large proportion of participants might receive a placebo alone.