TY  - JOUR
N1  - © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
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AV  - public
Y1  - 2021/07/31/
VL  - 22
EP  - 17
TI  - An Investigation of Levetiracetam in Alzheimer's Disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study
A1  - Sen, A
A1  - Akinola, M
A1  - Tai, XY
A1  - Symmonds, M
A1  - Jones, GD
A1  - Mura, S
A1  - Galloway, J
A1  - Hallam, A
A1  - Chan, JYC
A1  - Koychev, I
A1  - Butler, C
A1  - Geddes, J
A1  - Van Der Putt, R
A1  - Thompson, S
A1  - Manohar, SG
A1  - Frangou, E
A1  - Love, S
A1  - McShane, R
A1  - Husain, M
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Medicine
KW  -  Research & Experimental
KW  -  Research & Experimental Medicine
KW  -  Anti-seizure medication
KW  -  Cognition
KW  -  Dementia
KW  -  Epilepsy
KW  -  Levetiracetam
KW  -  Randomised controlled trial
KW  -  Pilot
KW  -  Proof of concept
KW  -  Seizure
KW  -  PARTIAL SEIZURES
KW  -  OLDER
KW  -  MULTICENTER
KW  -  COGNITION
KW  -  DEMENTIA
KW  -  DEFICITS
KW  -  BINDING
KW  -  TOLERABILITY
KW  -  EPILEPSY
KW  -  EFFICACY
JF  - Trials
UR  - https://doi.org/10.1186/s13063-021-05404-4
PB  - BMC
SN  - 1745-6215
N2  - Background:
Although Alzheimer?s disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer?s disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer?s disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer?s disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer?s disease.

Methods:
The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer?s disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values.

Discussion:
This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer?s disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, 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.

Trial registration:
ClinicalTrials.govNCT03489044. Registered on April 5, 2018.
ID  - discovery10133201
ER  -