AD-SMART: UK-wide phase 3 trials evaluating multiple treatments for clinical Alzheimer's disease

What is the aim of the study? 

The aim of AD-SMART is to test different medications for the treatment of Alzheimer’s disease by comparing them to a dummy medication (placebo). This study will look at how these medications affect memory and thinking, as well as the ability to carry out activities of everyday living, over time, with assessments carried out at regular points during the study.

What will participants be asked to do?  

Eligibility screening: not everyone may be able to take part in the study, therefore, we need to do some tests first to see whether you are able to take part. These are known as “eligibility screening tests’’. We will also do an eligibility test on your study partner by asking a few questions. 

Randomisation: if you’re eligible, and agree to take part, a computer will randomly assign you to one of the groups. You will receive either one of the two medications being tested or a dummy pill (placebo).  You, your study partner, or your doctor or study team will not know what medication you are receiving or if you are receiving the dummy pill. 

Study medication: the study medication will be posted to you, and you will continue with your usual care. AD-SMART is starting with medications that are already used for other conditions. These are called “repurposed” treatments. This means we already know they are safe to use, which can make the development of new treatments faster and more efficient. You will be asked to take medication every day according to a schedule for a maximum of 18 months.

The first AD-SMART medications are: 

• atomoxetine - currently used to treat Attention Deficit Hyperactivity Disorder (ADHD)
• metformin - currently used to treat a type of diabetes
• a dummy drug (called a placebo) which looks like the trial medication but does not contain any medicine - it is important to include a dummy drug in the trial design to allow a direct comparison of whether the other drugs are proving to be beneficial.

Study partner: you will need a study partner to take part in this study. This can be a family member or a close friend who knows you well. They will answer questions about how you’re doing at different points during the study. 

Future visits: as part of the study, you will have regular follow-up over a period of 18 months and your study partner will be attending these visits with you. You will be asked to come into the clinic at the start for screening tests. You will also be asked to come in when all the tests show that you are eligible to join the study to confirm that you are happy to continue and to complete some questionnaires and assessments. There will be phone or video calls at 3, 9 and 15 months to assess how you are getting along and whether you have missed any doses or experienced any side effects. There will be clinic visits in-person at 6, 12 and 18 months. During these in-person visits, a qualified person from the study team will take your blood for safety tests and additional study specific blood tests. You will be asked about how you are doing on the medication and whether you have missed any doses or experienced any side effects. You will also be asked to perform memory and thinking tasks.
You may be asked to have an MRI, if it is safe for you to do so, at your screening visit. At the end of the study, you will be asked to have another MRI.