Eli Lilly and Company, Indianapolis, IN, USA.
J Parkinsons Dis. 2022;12(6):1991-2004. doi: 10.3233/JPD-213126.
PRESENCE was a Phase 2 trial assessing mevidalen for symptomatic treatment of Lewy body dementia (LBD). Participants received daily doses (10, 30, or 75 mg) of mevidalen (LY3154207) or placebo for 12 weeks.
To evaluate if frequent cognitive and motor tests using an iPad app and wrist-worn actigraphy to track activity and sleep could detect mevidalen treatment effects in LBD.
Of 340 participants enrolled in PRESENCE, 238 wore actigraphy for three 2-week periods: pre-, during, and post-intervention. A subset of participants (n = 160) enrolled in a sub-study using an iPad trial app with 3 tests: digital symbol substitution (DSST), spatial working memory (SWM), and finger-tapping. Compliance was defined as daily test completion or watch-wearing ≥23 h/day. Change from baseline to week 12 (app) or week 8 (actigraphy) was used to assess treatment effects using Mixed Model Repeated Measures analysis. Pearson correlations between sensor-derived features and clinical endpoints were assessed.
Actigraphy and trial app compliance was > 90% and > 60%, respectively. At baseline, daytime sleep positively correlated with Epworth Sleepiness Scale score (p < 0.01). Physical activity correlated with improvement on Movement Disorder Society -Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II (p < 0.001). Better scores of DSST and SWM correlated with lower Alzheimer Disease Assessment Scale -Cognitive 13-Item Scale (ADAS-Cog13) (p < 0.001). Mevidalen treatment (30 mg) improved SWM (p < 0.01), while dose-dependent decreases in daytime sleep (10 mg: p < 0.01, 30 mg: p < 0.05, 75 mg: p < 0.001), and an increase in walking minutes (75 mg dose: p < 0.001) were observed, returning to baseline post-intervention.
Devices used in the LBD population achieved adequate compliance and digital metrics detected statistically significant treatment effects.
PRESENCE 是一项评估 mevidalen 治疗路易体痴呆（LBD）症状的 2 期试验。参与者接受每日剂量（10、30 或 75mg）的 mevidalen（LY3154207）或安慰剂治疗 12 周。
评估使用 iPad 应用程序和腕戴式活动记录仪跟踪活动和睡眠的频繁认知和运动测试是否可以检测到 LBD 中的 mevidalen 治疗效果。
在 PRESENCE 中招募的 340 名参与者中，有 238 名参与者佩戴活动记录仪进行了三个为期 2 周的阶段：干预前、干预中和干预后。一部分参与者（n=160）参加了一项使用 iPad 试验应用程序的子研究，该应用程序有 3 项测试：数字符号替代（DSST）、空间工作记忆（SWM）和手指敲击。依从性定义为每天完成测试或佩戴手表≥23 小时/天。使用混合模型重复测量分析评估从基线到第 12 周（应用程序）或第 8 周（活动记录仪）的治疗效果。评估传感器衍生特征与临床终点之间的 Pearson 相关性。
活动记录仪和试验应用程序的依从性分别超过 90%和 60%。在基线时，白天的睡眠与 Epworth 嗜睡量表评分呈正相关（p<0.01）。身体活动与运动障碍协会统一帕金森病评定量表（MDS-UPDRS）第二部分的改善相关（p<0.001）。DSST 和 SWM 的更好分数与更低的阿尔茨海默病评估量表-认知 13 项量表（ADAS-Cog13）相关（p<0.001）。Mevidalen 治疗（30mg）改善了 SWM（p<0.01），而白天睡眠减少（10mg：p<0.01，30mg：p<0.05，75mg：p<0.001）和行走分钟数增加（75mg 剂量：p<0.001）则呈剂量依赖性，干预后恢复到基线。
用于 LBD 人群的设备实现了足够的依从性，并且数字指标检测到了具有统计学意义的治疗效果。
