Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial
Abstract Objective To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure. Methods We performed a randomized, double‐blind, placebo‐controlled crossover pilot study in individuals wit...
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Wiley
2024-12-01
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| Series: | Epilepsia Open |
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| Online Access: | https://doi.org/10.1002/epi4.13070 |
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| author | Arjune Sen Sofia Toniolo Xin You Tai Mary Akinola Mkael Symmonds Sergio Mura Joanne Galloway Angela Hallam Jane Y. C. Chan Ivan Koychev Chris Butler John Geddes Gabriel Davis Jones Younes Tabi Raquel Maio Eleni Frangou Sharon Love Sian Thompson Rohan Van Der Putt Sanjay G. Manohar Rupert McShane Masud Husain |
| author_facet | Arjune Sen Sofia Toniolo Xin You Tai Mary Akinola Mkael Symmonds Sergio Mura Joanne Galloway Angela Hallam Jane Y. C. Chan Ivan Koychev Chris Butler John Geddes Gabriel Davis Jones Younes Tabi Raquel Maio Eleni Frangou Sharon Love Sian Thompson Rohan Van Der Putt Sanjay G. Manohar Rupert McShane Masud Husain |
| author_sort | Arjune Sen |
| collection | DOAJ |
| description | Abstract Objective To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure. Methods We performed a randomized, double‐blind, placebo‐controlled crossover pilot study in individuals with mild‐to‐moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up‐titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down‐titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires. Results Recruitment numbers were severely limited owing to restrictions from the COVID‐19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task. Significance This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease. Plain Language Summary Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with Alzheimer's disease (the most common cause of dementia). In this pilot study, we could not prove whether levetiracetam helped memory function. We did show that the drug is safe and well tolerated in people with dementia who have not had a seizure. This work, therefore, offers a platform for future research exploring antiseizure medications in people with dementia. |
| format | Article |
| id | doaj-art-eb86af874efe4e29acd0d7512a1d6fbe |
| institution | DOAJ |
| issn | 2470-9239 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj-art-eb86af874efe4e29acd0d7512a1d6fbe2025-08-20T02:50:04ZengWileyEpilepsia Open2470-92392024-12-01962353236410.1002/epi4.13070Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trialArjune Sen0Sofia Toniolo1Xin You Tai2Mary Akinola3Mkael Symmonds4Sergio Mura5Joanne Galloway6Angela Hallam7Jane Y. C. Chan8Ivan Koychev9Chris Butler10John Geddes11Gabriel Davis Jones12Younes Tabi13Raquel Maio14Eleni Frangou15Sharon Love16Sian Thompson17Rohan Van Der Putt18Sanjay G. Manohar19Rupert McShane20Masud Husain21Oxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences John Radcliffe Hospital Oxford UKDepartment of Neurology John Radcliffe Hospital Oxford UKOxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences John Radcliffe Hospital Oxford UKLocal Clinical Trials Network John Radcliffe Hospital Oxford UKOxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences John Radcliffe Hospital Oxford UKClinical Trials Pharmacy John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust Oxford UKCPSU Oxford Health Foundation Trust Oxford UKSt Mary's Pharmaceutical Unit Cardiff University Cardiff UKFreeline Therapeutics King's Court Stevenage UKDepartment of Psychiatry University of Oxford Oxford UKFaculty of Medicine, Department of Brain Sciences Imperial College, Sir Alexander Fleming Building, South Kensington Campus London UKDepartment of Psychiatry University of Oxford Oxford UKOxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences John Radcliffe Hospital Oxford UKDepartment of Neurology University Hospital of Kiel Kiel GermanyNuffield Department of Clinical Neuroscience University of Oxford Oxford UKMRC Clinical Trials Unit at UCL, Faculty of Pop Health Sciences Institute of Clinical Trials & Methodology, University College London London UKMRC Clinical Trials Unit at UCL, Faculty of Pop Health Sciences Institute of Clinical Trials & Methodology, University College London London UKDepartment of Neurology John Radcliffe Hospital Oxford UKMemory and Cognition Research Delivery Team Warneford Hospital Oxford UKDepartment of Neurology John Radcliffe Hospital Oxford UKDepartment of Psychiatry University of Oxford Oxford UKDepartment of Neurology John Radcliffe Hospital Oxford UKAbstract Objective To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure. Methods We performed a randomized, double‐blind, placebo‐controlled crossover pilot study in individuals with mild‐to‐moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up‐titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down‐titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires. Results Recruitment numbers were severely limited owing to restrictions from the COVID‐19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task. Significance This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease. Plain Language Summary Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with Alzheimer's disease (the most common cause of dementia). In this pilot study, we could not prove whether levetiracetam helped memory function. We did show that the drug is safe and well tolerated in people with dementia who have not had a seizure. This work, therefore, offers a platform for future research exploring antiseizure medications in people with dementia.https://doi.org/10.1002/epi4.13070antiseizure medicationsdementiaepilepsyOxford Memory Testseizure |
| spellingShingle | Arjune Sen Sofia Toniolo Xin You Tai Mary Akinola Mkael Symmonds Sergio Mura Joanne Galloway Angela Hallam Jane Y. C. Chan Ivan Koychev Chris Butler John Geddes Gabriel Davis Jones Younes Tabi Raquel Maio Eleni Frangou Sharon Love Sian Thompson Rohan Van Der Putt Sanjay G. Manohar Rupert McShane Masud Husain Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial Epilepsia Open antiseizure medications dementia epilepsy Oxford Memory Test seizure |
| title | Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial |
| title_full | Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial |
| title_fullStr | Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial |
| title_full_unstemmed | Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial |
| title_short | Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double‐blind placebo‐controlled crossover trial |
| title_sort | safety tolerability and efficacy outcomes of the investigation of levetiracetam in alzheimer s disease iliad study a pilot double blind placebo controlled crossover trial |
| topic | antiseizure medications dementia epilepsy Oxford Memory Test seizure |
| url | https://doi.org/10.1002/epi4.13070 |
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