NCT03489044

An Investigation of Levetiracetam in Alzheimer's Disease

An Investigation of Levetiracetam in Alzheimer's Disease (ILiAD): a Proof of Concept Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

The study proposed aims to evaluate the effect of Levetiracetam in patients with Alzheimer's disease (AD) in a Phase 2 Clinical Trial. Levetiracetam is an established anti-epileptic medication that has been approved by NICE (UK) as a first line treatment for focal epilepsy. Levetiracetam is now generic and acts, as all anti-epileptic medications do, by stabilising neuronal networks. However, Levetiracetam appears unique amongst the anti-epileptic medications in being able to stabilise aberrant neuronal networks in Alzheimer's disease. In both animal models of AD and in patients with mild cognitive impairment, Levetiracetam can offer benefit to cognition. The investigators therefore aim to test whether Levetiracetam, through stabilisation of neuronal networks, may offer benefit to cognition in patients with AD.

Detailed description

Lay 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 people with Alzheimer's disease and people 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 people 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 Health and Care 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. The investigators wish to allocate thirty patients with Alzheimer's disease with no history of previous seizure 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. The effect that Levetiracetam has on memory in Alzheimer's disease will be studied using several standardised scales. Tests that the investigators 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 study evaluates 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. Main hypothesis: 1. Treatment with the anti-epileptic drug Levetiracetam will be of benefit to cognitive deficits in Alzheimer's disease because electrophysiological disruption of neuronal networks contributes to the pathophysiology of the condition. 2. Treatment with Levetiracetam at a dose that is routinely utilized in older people with epilepsy will be well tolerated in patients with Alzheimer's disease and, in particular, will not adversely affect mood 3. Electroencephalography (EEG) may offer a biomarker to predict which patients with Alzheimer's disease might be especially suited to treatment with Levetiracetam

Conditions

• Alzheimer Disease
• Epilepsy

Interventions

Type	Name	Description
DRUG	Levetiracetam	To up-titrate Levetiracetam to 500mg (two tablets) twice daily followed by maintenance on Levetiracetam 500mg twice daily for four weeks and then down-titrate to nil over four weeks
DRUG	Placebo Oral Tablet	To up-titrate placebo to two tablets twice daily followed by maintenance on placebo two tablets twice daily for four weeks and then down-titrate to nil over four weeks

Timeline

• Start date: 2018-10-28
• Primary completion: 2022-03-21
• Completion: 2022-03-21
• First posted: 2018-04-05
• Last updated: 2024-04-24

Locations

1 site across 1 country: United Kingdom