A clinical trial has begun in the United Kingdom with the aim of accelerating the discovery of new treatments for Alzheimer's disease. According to BBC News, the study will evaluate multiple drugs at the same time, beginning with two repurposed medications already in use for type 2 diabetes and attention deficit hyperactivity disorder.
The trial, known as AD-SMART, will investigate whether these drugs can reduce symptoms including memory loss and cognitive decline, while helping participants preserve their independence and quality of life. Angela Bucksey, aged 67 from Cambridgeshire, received an Alzheimer's diagnosis in January and became the first participant to enrol in the study.
Bucksey described her family's history with the disease and her decision to participate.
We have Alzheimer's in the family. My mother had it and my aunts, so it was a disappointment rather than a shock when I was diagnosed because I knew it would restrict my life. But I was determined that it wasn't going to define me.She explained that joining the trial gave her a sense of agency.
Instead of just sitting there, you're standing up and saying, I will fight back.
Alzheimer's remains the leading cause of dementia in the UK, affecting approximately 600,000 individuals. Prime Minister Andy Burnham, whose father died from Alzheimer's last month, expressed his commitment to the research effort.
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.Burnham acknowledged the personal toll the disease takes on families.
How does the trial design work?
The AD-SMART study employs a multi-arm, multi-stage platform trial structure, meaning several treatments are tested simultaneously with results compared against a control group receiving a placebo. This approach increases the probability that participants will receive an active treatment compared with conventional trial designs. If a drug fails to demonstrate benefit, it can be withdrawn quickly and replaced with a new candidate—a method that has proven effective in cancer and motor neurone disease research.
The two initial drugs under investigation are metformin, a standard type 2 diabetes medication, and atomoxetine, used to treat ADHD. An international panel of experts selected both compounds based on their potential to reduce brain inflammation, a key driver of neurodegeneration. According to the trial protocol, metformin dosing begins at 500 mg in week one and increases to 2,000 mg daily from week four, while atomoxetine is administered as 25 mg capsules.
Prof Paresh Malhotra, chief investigator and group leader at the UK Dementia Research Institute Centre for Care Research & Technology at Imperial College London, explained the rationale for this approach.
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.
What outcomes will the trial measure?
For the drugs to be considered successful, the study must demonstrate beneficial effects on thinking ability and the capacity to perform daily activities.
That's what patients and their carers care about,Prof Malhotra stated. According to the trial protocol, the co-primary measures are change in cognition assessed using the ADAS-Cog scale and daily function measured by the Amsterdam IADL Questionnaire. The study will also evaluate caregiver burden, quality of life, safety, and health-economic outcomes.
All participants will undergo regular health assessments including cognitive testing to enable researchers to evaluate treatment effectiveness. The trial plans to recruit 1,200 people aged 55 or older with biomarker-confirmed Alzheimer's or mixed Alzheimer's and vascular dementia, with participants followed for 18 months. The overall study is expected to run until March 2031, with scientists anticipating completion of evaluation for the first drugs by 2030.
Where is the trial taking place?
More than 30 sites across the UK are participating in the recruitment process. Sites in Cambridgeshire, Surrey, London, Southampton and Edinburgh are already operational. People with a confirmed Alzheimer's diagnosis who wish to participate can register their interest through the AD-SMART website.
What do participants and their families say?
Angela Bucksey's husband Steve, who serves as her study partner, described the emotional impact of participation.
Joining the trial has brought us back from the despair of a diagnosis which everybody recognises is non-recoverable. People who know we are on a drug trial understand that we're doing something about it and, rather than be sorry for us, they can be encouraging.
Dr Sheona Scales, director of research at Alzheimer's Research UK, emphasised the urgency of developing new options.
Time is precious for people living with Alzheimer's disease and more treatment options are urgently needed.
What happens next?
Scientists expect to complete evaluation of the first drugs by 2030, and additional treatments are likely to be added to the trial during this period. In the drug-prioritisation process for future trial arms, atomoxetine ranked first and metformin second; levetiracetam and isorbide mononitrate tied for third and are due to be reconsidered alongside new proposals, according to the drug-prioritisation research. A UK-wide call for proposals for digital outcome measures was open until 30 August 2026, with the proposed tools intended as secondary measures alongside the trial's cognition and daily-function outcomes. The Alzheimer's Research UK drug-prioritisation programme is also seeking nominations for candidates that could be considered for future AD-SMART arms.
The trial is being led by the UK Dementia Research Institute and Alzheimer's Research UK, with partners including the National Institute for Health and Care Research, the Medical Research Council and Health Data Research UK, and funding provided by the UK government.
