Novel Methods for Clinical Trials in Dementia and Cognitive Decline

摘要： 我们将进行一项开放标记的双盲分组临床试验，检测血清“脂肪因子”蛋白。 作为美国联邦药品监督管理局(FDA)批准的药物多奈哌齐(Aricept®)的调解人S效应 关于潜在痴呆症严重程度指标“δ”。脂肪因子是由脂肪组织释放的炎性蛋白。 最近还与认知能力下降有关。我们的目的是展示在以下方面的多个潜在改进 未来任何与痴呆症相关的临床试验的进行。例如，使用电话评估 将招募和评估成本降至最低，并保护参与者免受潜在的SARS-Cov-2感染。 如果有必要，可以通过电话对未接种疫苗的受试者实施整个方案。 SARS-Cov-2。在之前的工作中，我们已经建立了潜在变量“δ”(痴呆症)作为痴呆症特有的 认知表型。我们将使用δ将研究小组的基线痴呆症严重程度等同起来，并设置 招募阈值以最大限度地提高逆转δ的S痴呆症转换阈值的潜力 如果治疗有效的话。我们将采用一种新的“身份线(LOI)”算法来进一步选择大多数案例 可能从我们的干预中受益(精准医学的一个例子)。我们将使用第二个潜伏期 痴呆症严重程度指标(DTEL)作为痴呆症的综合结果。最后，我们将测试一种潜在的 脂肪因子生物标记物作为多奈哌齐对δ影响的中介。这可能会建立一部小说 乙酰胆碱酯酶抑制机制。

Abstract: We will conduct an open-label double-blind group assignment clinical trial testing serum “adipokine” proteins as the mediators of the Federal Drug Administration (FDA)-approved medication donepezil (Aricept®)’s effect on the latent dementia severity metric “δ”. Adipokines are inflammatory proteins released by adipose tissues and recently associated with cognitive decline. Our intent is to demonstrate multiple potential improvements in the conduct of any future dementia-related clinical trial. For example, the use of telephone assessment minimizes recruitment and assessment costs and protects participants from potential SARS-cov-2 exposure. The entire protocol could be administered by telephone, if necessary, in subjects unvaccinated against SARS-cov-2. In prior work, we have established the latent variable “δ” (for dementia) as a dementia-specific cognitive phenotype. We will use δ to equate study groups on their baseline dementia severity and set the recruitment threshold to maximize the potential for reversions back across δ’s dementia conversion threshold if treatment is effective. We will deploy a novel “Line of identity (LOI)” algorithm to further select cases most likely to benefit from our intervention (an example of precision medicine). We will use a second latent dementia severity metric (dTEL) as a comprehensive dementia-specific outcome. Finally, we will test a latent adipokine biomarker construct as a mediator of donepezil’s effect on δ. That will potentially establish a novel mechanism for acetylcholinesterase inhibition.