New UK Trial Tests Repurposed Drugs for Alzheimer’s

A UK trial that will test several potential Alzheimer’s disease treatments at the same time has launched, with organisers saying its design could cut years from the search for effective therapies.The Alzheimer’s disease Systematic Multi-arm Adaptive Randomised Trial (AD-SMART), a platform trial that organisers describe as the first of its kind in Alzheimer’s, will test potential drugs simultaneously. It will begin with two repurposed medicines already used to treat attention-deficit/hyperactivity disorder and type 2 diabetes.Two Repurposed Drugs Go First Atomoxetine and metformin will be trialled first to assess whether the medicines can lessen symptoms of Alzheimer’s disease, such as memory and thinking problems, and help people maintain their quality of life as the disease progresses.Both drugs may help to reduce brain inflammation, which is a driver of neurodegeneration, said Professor Paresh Malhotra, chief investigator of AD-SMART and group leader at the UK Dementia Research Institute (UK DRI) Centre for Care Research & Technology at Imperial College London, speaking at a Science Media Centre briefing.“For too long, Alzheimer’s research has moved at the pace of one drug, one trial, one answer, sometimes taking a decade or more before we know if we’ve found something that works,” he said. “We are applying advances from cancer and other conditions to accelerate testing of treatments for people with Alzheimer’s disease. The way AD-SMART is set up means we’re testing several treatments at the same time, and those that don’t show promise can be quickly stopped. Then we can start testing something else. That’s the best way to get effective treatments to patients as quickly as we can.”The two drugs were chosen by an international panel of experts together with people with lived experience of Alzheimer’s, based on evidence from early-stage studies in patients as well as laboratory research. People with lived experience, working with a team at the University of Cambridge, have shaped the trial throughout its design, including which drugs to test and how success will be measured.Recruiting Across the UK Alzheimer’s is the most common type of dementia, affecting around 600,000 people in the UK. One of the issues with research into potential treatments for the disease is that too few people are recruited to trials. AD-SMART aims to change this and plans to recruit 1200 patients aged 55 or over with a confirmed diagnosis of Alzheimer’s, or mixed Alzheimer’s and vascular dementia.The first trial participants have been recruited at Cambridgeshire and Peterborough NHS Foundation Trust and Surrey and Borders Partnership NHS Foundation Trust. Sites at Imperial College Healthcare NHS Trust, the Anne Rowling Regenerative Neurology Clinic in Edinburgh, and in Southampton are already open. Up to 20 NHS sites are expected to open across the UK over the next 12-18 months, with more than 30 planned overall.Heather Ransome, 67, was diagnosed with Alzheimer’s in 2024 and is one of the first AD-SMART trial participants. Before her diagnosis, she and her partner enjoyed cruises and coach holidays in retirement. She said she is worried about her condition getting worse but that the trial has given her hope for the future.“I’m not the sort of person who gets upset, but being told you have Alzheimer’s is quite upsetting,” she said. “There weren’t many treatment options available, and the one drug I was offered has been around for many years. Getting involved with AD-SMART has given me some hope for the future,” she added. “It’s not too taxing, just some extra tablets to take every day. I don’t know whether I’m being given the active treatment, but if it helps me, or helps others in the future, that feels positive. I would encourage anyone who thinks they might be eligible to sign up and speak to the team.”Room for New Drugs Along the Way The trial will also introduce new drugs as they become available because of the way SMART trials are set up.“We already know this model works,” said Professor Siddharthan Chandran, director of the UK DRI. “The SMART approach, used by MND-SMART (a similar platform trial for motor neuron disease) has shown that testing multiple drugs at once, in one smart trial design, can speed up the testing of new treatments for neurodegenerative conditions. Now, we’re doing the same for Alzheimer’s. And because of the way SMART trials are designed, biotech and pharmaceutical companies can also bring their drugs straight into the trial. That means more treatments can be tested more quickly, and for people living with Alzheimer’s, that could make all the difference.”The AD-SMART team expect to finish evaluating the first drugs in 2030, and expect additional drugs to be added to the trial during that period.Julie Penfold is a freelance journalist specialising in healthcare and medical content. Her work regularly appears in titles such as Medscape, Doctors.net.uk, and Hospital Healthcare Europe.