Phase 2a Levetiracetam Trial for AD-Associated Network Hyperexcitability
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Changes in Executive Function as Measured by the NIH EXAMINER Computer Battery
研究概览
简要总结
Patients with Alzheimer's disease (AD) can have seizures in addition to losing their memory and other mental functions (referred to as cognitive functions). The seizures, and other examples of overactive electrical activity in the brain that is not noticeable, contribute to the loss of cognitive function. Studies in animal models of AD suggest that a drug that prevents seizures called levetiracetam may reduce neuronal over-excitation and improve cognition. Based on this evidence, the investigators propose to determine if levetiracetam can be used to treat patients with AD. The investigators developed novel instruments for this population that will also be used in future large-scale clinical trials.
The current study will last for 12 weeks and will involve people with AD. Participants will be initially examined with an overnight brain wave study to assess for silent epileptic (seizure-like) activity. Presence of epileptic activity on the screening exam is not required to enter the trial. Participants will then be assigned to groups in a randomized manner. One group will receive levetiracetam for 4 weeks, then no drug for 4 weeks, and then placebo for 4 weeks. For another group, the order of treatments will be reversed. The cognitive abilities of participants will be retested every 4 weeks and compared to those at the beginning. The cognitive tests include a virtual-reality navigation test of memory and computerized tests of mental flexibility and problem solving. The participants will be monitored with a magnetoencephalogram (MEG) with simultaneous EEG (M/EEG) at each visit. M/EEG is a highly effective non-invasive method for identifying brain regions of epileptic activity. The investigators will need to recruit 36 randomized participants to test the study hypotheses. This study will take place at the University of California, San Francisco (UCSF) and the University of Minnesota.
详细描述
For a more detailed explanation of the study and what our results were, please read our publication at https://jamanetwork.com/journals/jamaneurology/fullarticle/2784539
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Levetiracetam-Placebo
This group receives levetiracetam for 4 weeks twice daily, then has a break where no treatment is given for 4 weeks, and then receives placebo for 4 weeks.
干预措施: levetiracetam (Drug)
Placebo-Levetiracetam
This group receives placebo for 4 weeks twice daily, then has a break where no treatment is given for 4 weeks, and then receives levetiracetam for 4 weeks.
干预措施: levetiracetam (Drug)
结局指标
主要结局
Changes in Executive Function as Measured by the NIH EXAMINER Computer Battery
时间窗: Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment)
Changes in executive function were measured using the NIH EXAMINER, a 1-hour computer-based battery of various executive function tasks. The subject's performance after the study treatment will be compared with results from a baseline assessment done before the study treatment, using statistical tests to assess whether there was any significant change. The Examiner assessment consists of the following scales: antisaccade , set shifting , flanker task, dot counting, spatial 1-back, category fluency, and letter fluency. Scores for this task have an indefinite range. Higher scores however do indicate better performance. Scores for this scale were generated using item response theory. For this study, scores with SEs greater than 0.55 were classified as unreliable and excluded from analysis. Composite scores from 2 participants were excluded on this basis.The EXAMINER ranges for the participants in the study were -2.59 to 1.33.
次要结局
- Changes in Stroop Interference Naming(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))
- Changes in ADAS-cog(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))
- Changes in Behavior and Level of Disability - ADCS-ADL(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))
- Clinical Dementia Rating Sum of Boxes (CDR-SOB)(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))
- Changes in Behavior and Level of Disability - ADCS-CGIC(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))
- Changes in Behavior and Level of Disability - Neuropsychiatric Inventory (NPI)(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))
- Changes in Epileptiform Events(Difference between weeks 0-4 (Baseline) and weeks 8-12 (Treatment))