A first-of-its-kind clinical trial has launched in the UK, which could cut years from the search for treatments that work for people with Alzheimer’s disease. The national trial, called AD-SMART (Alzheimer’s disease Systematic Multi-arm Adaptive Randomised Trial), is led by Prof Paresh Malhotra at the UK DRI.
AD-SMART will test multiple drugs simultaneously, starting with two repurposed medicines already used to treat type 2 diabetes and attention deficit hyperactivity disorder (ADHD). Groups of participants will each begin treatment with a different drug. The study will examine whether these medicines can lessen symptoms such as memory and thinking problems and help people maintain their quality-of-life as the disease progresses.
Testing drugs that are already approved to treat other conditions and known to be safe means that, if successful, treatments can reach people living with Alzheimer’s much faster than a medicine developed from scratch.
It is funded by the UK DRI and Alzheimer's Research UK in partnership with the National Institute for Health and Care Research (NIHR), the UKRI Medical Research Council (MRC) and Health Data Research UK (HDR UK). Ongoing funding has been committed by UK government to support the trial.
Heather with her partner Roger
Heather Ransome, 67, from the Isle of Wight, was diagnosed with Alzheimer’s in 2024. She said:
“Before my diagnosis, my partner and I were going on lots of cruises and coach holidays, enjoying retirement together. We still enjoy life, but I’m worried about my condition getting worse.
“I’m not the sort of person who gets upset, but being told you have Alzheimer’s is quite upsetting. 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. 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 future, that feels positive. I would encourage anyone who thinks they might be eligible to sign up and speak to the team.”
I know how it feels to lose a loved one to dementia and have seen first-hand the devastating impact this illness has on families. That's why I’m proud to see this trial being launched in the UK, so that cutting edge treatments can reach patients here as soon as possible. I have made dementia research a national priority. I want Britain to be the leading nation, making the breakthroughs that change people’s lives.
The Prime Minister
AD-SMART is a type of trial known as a multi-arm, multi-stage platform trial. Several drugs are tested at the same time, and the results compared with one group of participants taking a dummy drug (placebo). This means more people receive an active treatment than would in a traditional trial.
Results are checked at regular stages throughout the trial and any drug that isn’t showing benefit can be dropped quickly, with new drugs added in its place. Overall, this means fewer participants end up receiving ineffective drugs.
Testing several drugs against one shared placebo group means that ̶̶̶compared with a traditional trial, the time to evaluate treatments can be more than halved, which also reduces costs.
The trial is being delivered by a team at Imperial College London, the UCL Innovative Clinical Trials Unit and the MRC Centre of Research Excellence in Clinical Trial Innovation (UCL), the University of Oxford and Dementias Platform UK (DPUK), with support from leading Alzheimer's experts from across the UK.
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. 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 first trial participants have been recruited at Cambridgeshire and Peterborough NHS Foundation Trust and Surrey and Borders Partnership NHS Foundation Trust, and sites based at Imperial College Healthcare NHS Trust, Edinburgh and Southampton are now open. Up to 20 NHS sites are expected to open across the UK over the next 12-18 months and more than 30 are planned overall. Researchers aim to recruit 1,200 participants across the UK to test these first two drugs. They expect to finish evaluating the first drugs in 2030, in around four years’ time. During this initial four-year period, the team expect additional drugs to be added into the trial for testing.
AD-SMART is the first trial of this kind for people living with Alzheimer's, but the model has already proven itself in the UK. MND-SMART, a similar platform trial for motor neuron disease, also led by the UK DRI, concluded that its first drugs tested were ineffective in just over three years - a process that would normally take at least eight. The trial has now moved on to testing other promising drugs.
Professor Siddharthan Chandran, Director of the UK Dementia Research Institute, said:
“We already know this model works. The SMART approach, used by MND-SMART, 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 tested more quickly, and for people living with Alzheimer’s, that could make all the difference.”
The two starting drugs were carefully chosen by an international panel of experts, together with people with lived experience of Alzheimer’s, based on evidence from earlier 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, which drugs to test and how success is measured.
People with a confirmed Alzheimer’s diagnosis who would like to take part can register their interest by:
- contacting the AD-SMART recruitment co-ordinator at adsmart@psych.ox.ac.uk or on 01865 283806;
- contacting the Alzheimer’s Research UK Infoline at infoline@alzheimersresearchuk.org or on 0300 111 5111
To take part in this study and find other opportunities to participate in groundbreaking trials, visit Join Dementia Research.
Alzheimer’s is the most common type of dementia, affecting around 600,000 people in the UK. There are currently no NHS treatments that can slow or stop the underlying disease.
Dr Sheona Scales, Director of Research at Alzheimer’s Research UK said:
“For people living with Alzheimer's disease, time is precious. We urgently need more treatment options that can help people live better for longer and stay connected to the people they love.
“AD-SMART offers a smarter, faster way than conventional trials to find out which treatments could make a real difference. It’s the kind of innovative trial that Alzheimer’s Research UK’s Clinical Accelerator Programme was set up to support; AD SMART is the first trial we’ve funded via the programme.
“We hope this new approach to clinical trials will could help bring a future closer where people affected by Alzheimer’s have more treatment options — and ultimately, a cure.”
Professor Sir Andrew Morris, Director of Health Data Research UK, said:
“We urgently need faster ways to test potential treatments for dementia and Alzheimer’s disease. The AD-SMART trial is a great example of how we can do this by testing several treatments at once and quickly moving on from those that don’t show benefit. Through the Dementia Trials Accelerator, led by HDR UK and the UK Dementia Research Institute, we are building the data and trial infrastructure needed to make dementia research faster and more efficient, helping promising treatments reach people sooner.”
Professor Lucy Chappell, Chief Scientific Adviser to the Department of Health and Social Care and CEO of the NIHR, said:
"For 20 years, the NIHR has empowered experts to tackle some of the biggest challenges in health and care, ensuring research reaches the people who need it most.
“I am delighted to welcome the launch of AD-SMART, a ground-breaking trial that will accelerate the testing of potential treatments for people affected by Alzheimer’s. It is a prime example of the ambitious, innovative research we need, which is why the NIHR has committed to its ongoing support as it opens more sites across the UK.
“AD-SMART will also play an important role in our ambition to increase participation in dementia clinical trials across the UK, strengthening our ability to test new treatments. Together, our investments aim to bring the benefits of research to people with dementia and their families sooner."
Science Minister, Chris McDonald MP said:
"Dementia has a devastating impact on millions of people, both for those living with the illness and for their friends and families. There is still so much we need to learn about how this disease works so we can then find the best ways to treat it, but this programme can help us bridge the gap.
“AD-SMART will help to uncover potential new treatments faster by exploring how existing drugs might be used to treat dementia, giving hope that we might be able to find ways to improve patients’ quality of life in the future.”
Minister of State for Social Care and Mental Health Alison McGovern said:
“With an ageing population we need to change the way we look after people with dementia, and we can do this with a plan combining science and a new social care service together.
“Research gives us the tools we need to fight against dementia, and I welcome the launch of this first-of-its-kind innovative trial testing multiple treatments simultaneously and looking to speed up the process. To support more clinical studies, we have invested £33 million into the Dame Barbara Windsor Dementia Goals programme.
“We will build a National Care Service that will transform social care, including better support for people living with dementia and their families. As recommended by Baroness Casey's commission on reform of the social care system, we are appointing a National Dementia Tsar to help drive forward that progress, and we are publishing the first ever Modern Service Framework for Frailty and Dementia to deliver rapid improvements in quality of care."
MRC Executive Chair Professor Patrick Chinnery said:
"Innovative clinical trials like AD-SMART are crucial to accelerating progress in health research, generating robust evidence at pace and supporting faster translation of research into patient benefit. This is particularly important in dementia and Alzheimer's disease research, where there is an urgent clinical need for new therapeutic options.
This UK DRI-led trial draws on expertise across the MRC’s institutes, the MRC Centre of Research Excellence in Clinical Trial Innovation, and the Dementia Trials Accelerator, which speeds up recruitment into clinical trials, to evaluate promising interventions more rapidly, and hopefully bring new treatment options to the people who need them."
AD-SMART
For more information on the trial and how to register interest, visit the AD-SMART website.
