The ILiAD Study
Research type
Research Study
Full title
An investigation of Levetiracetam in Alzheimer’s Disease (ILiAD): a proof of concept study
IRAS ID
203849
Contact name
Arjune Sen
Contact email
Sponsor organisation
University of Oxford
Eudract number
2016-003109-32
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary
Alzheimer’s disease affects around 800,000 people in the UK alone and costs almost £23 billion per year. The only currently licensed treatments for Alzheimer’s disease offer modest benefit at best. Seizures are more common in patients with Alzheimer’s disease and patients with Alzheimer’s disease may also have evidence of abnormal brainwave activity without having obvious seizures. Seizures may contribute to the loss of nerve cells and abnormal brainwave activity can disrupt thinking and memory. This abnormal electrical activity is therefore a potentially important drug target.
The anti-epileptic drug Levetiracetam can reduce abnormal brainwave activity and reverse memory deficits in a mouse model of Alzheimer’s disease. Levetiracetam can also improve memory difficulties seen in patients with mild cognitive impairment, a pre-cursor to Alzheimer’s disease. Clinical use of Levetiracetam is already widespread and it is recommended by The National Institute of Clinical and Healthcare Excellence as a first line treatment for seizures. Levetiracetam is generic (off-patent), is not known to interact with any other drugs and is well tolerated. A promising, cheap and safe approach might be to use Levetiracetam as a treatment to help with memory difficulties in Alzheimer’s disease.
The proposed project is a proof of concept study. We wish to recruit thirty patients with Alzheimer’s disease with no history of previous seizure and allocate them to initially receive either Levetiracetam or placebo before patients ‘cross-over’ so that the participants who initially received Levetiracetam are then given placebo and vice-versa (please see attached flowsheet). The effect that Levetiracetam has on memory in Alzheimer’s disease will be studied using several standardised scales. Tests that we have developed to better detect subtle improvements in thinking will also be used. Patients will have a straightforward, non-invasive test called an electroencephalogram to look at their brainwave activity at the start of the study as there may be brainwave markers that might help to predict which patients would benefit most from Levetiracetam.
This is the first study to evaluate if an anti-epileptic medication can offer meaningful benefit to patients with Alzheimer's disease. If this study is successful, the next step will be to rapidly progress to a larger study to establish whether Levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease.
Summary of Results
Background:
More and more we understand that there may be an intersection between epilepsy, a condition characterised by spontaneous recurrent seizures, and Alzheimer’s disease. This offers a potential therapeutic opportunity.
We thought that stabilising nerve cell networks would likely offer a benefit to memory. We therefore began a pilot study to explore whether the anti-seizure medication levetiracetam might offer benefit to people with Alzheimer’s disease.Methods:
The Investigation of Levetiracetam in Alzheimer’s Disease (ILiAD) trial recruited people with mild to moderate Alzheimer’s disease who have not previously had a seizure and in whom a routine test of brain wave activity (an electroencephalogram) was normal. We compared levetiracetam to placebo in this patient population. Neither investigators nor participants knew whether a participant was receiving the active drug (levetiracetam) or the placebo.
The main outcome that we looked for was a change in how somebody performed on a computer based touchscreen task. We also studied effect on mood, alterations in quality of life and carer-reported outcomes.Results:
We had planned to recruit 30 participants. Regrettably, owing to the COVID-19 pandemic the trial had to halt prematurely. In total eight people completed both arms of the study with no withdrawals from those enrolled. We could not fully assess whether levetiracetam did offer benefit to cognition. We did show that levetiracetam did not associate with side effects in this patient group.Conclusion:
ILiAD is a pilot study that is part of the vanguard of trials exploring the potential role of anti-seizure medications, particularly levetiracetam, in people with Alzheimer’s disease. Although we cannot say whether levetiracetam helps with memory in people with dementia or not, given that the medication was well tolerated, this study should offer the foundation for larger studies to see if anti-seizure medications can help in the treatment of dementia.REC name
South Central - Oxford B Research Ethics Committee
REC reference
17/SC/0468
Date of REC Opinion
8 Nov 2017
REC opinion
Further Information Favourable Opinion