HealthPartners Center for Memory and Aging, 295 Phalen Boulevard, Saint Paul, MN, 55130, USA.
HealthPartners Institute, Bloomington, MN, USA.
Drugs Aging. 2021 May;38(5):407-415. doi: 10.1007/s40266-021-00845-7. Epub 2021 Mar 15.
Intranasal insulin is a potential treatment for neurodegenerative disease shown to increase cerebral glucose uptake, reduce amyloid plaques, and improve verbal memory in cognitively impaired as well as healthy adults. Investigations have suggested rapid-acting insulins such as glulisine may result in superior cognitive benefits compared with regular insulin.
The aim of this study was to evaluate the safety and efficacy of rapid-acting intranasal glulisine in subjects with amnestic mild cognitive impairment (MCI) or mild probable Alzheimer's disease (AD).
We performed a single-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy of intranasal glulisine 20 IU twice daily versus saline placebo in 35 memory-impaired (MCI/AD) subjects using the Impel NeuroPharma I109 Precision Olfactory Delivery (POD) device. The 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), Clinical Dementia Rating (CDR) global score, and Functional Assessment Questionnaire (FAQ) were measured at baseline and 3 and 6 months. Secondary outcome measures included digit span forward/backwards, Trail Making Test Parts A/B, Controlled Oral Word Association Test (COWAT), and Weschler Memory Scale (WMS)-IV logical memory. Adverse effects (AEs) and serious adverse effects (SAEs) were measured along with blood glucose/insulin levels.
No significant difference in ADAS-Cog13, CDR Sum of Boxes (CDR-SOB), or FAQ scores were found between treatment groups at 3 and 6 months. Subjects in the saline group were significantly older than those in the glulisine group (p = 0.022). No significant differences in sex, education, apolipoprotein E4 (ApoE4) status, and Montreal Cognitive Assessment (MoCA) score existed between treatment groups. Overall, the number of adverse events per person was similar between groups (2.32 vs. 2.24; p = 0.824), although subjects receiving intranasal glulisine had higher rates of nasal irritation (25.0% vs. 13.9%) and respiratory symptoms (15.9% vs. 8.3%) compared with placebo. There were no differences in blood sugar or rate of hypoglycemia between the treatment and placebo groups.
Intranasal glulisine was relatively safe and well-tolerated and did not consistently impact peripheral glucose or insulin levels. There were no enhancing effects of intranasal glulisine on cognition, function, or mood, but the ability to detect significance was limited by the number of subjects successfully enrolled and the study duration. CLINICALTRIALS.
NCT02503501.
鼻内胰岛素是一种有潜力的治疗神经退行性疾病的方法，已被证明可增加大脑葡萄糖摄取、减少淀粉样斑块，并改善认知障碍和健康成年人的言语记忆。研究表明，与常规胰岛素相比，速效胰岛素如格鲁辛可能会带来更好的认知益处。
本研究旨在评估每日两次使用快速作用鼻内格鲁辛在有遗忘型轻度认知障碍（MCI）或轻度可能的阿尔茨海默病（AD）的受试者中的安全性和疗效。
我们进行了一项单中心、随机、双盲、安慰剂对照研究，使用 ImpelNeuroPharma I109 精密嗅觉输送（POD）装置，评估每日两次 20 IU 鼻内格鲁辛与盐水安慰剂在 35 名记忆受损（MCI/AD）受试者中的疗效。使用 Alzheimer 病评估量表认知分量表（ADAS-Cog13）、临床痴呆评定量表（CDR）总体评分和功能评估问卷（FAQ）在基线和 3 个月及 6 个月时进行测量。次要终点包括数字跨度向前/向后、连线测试 A/B 部分、受控口头联想测验（COWAT）和韦氏记忆量表（WMS）-IV 逻辑记忆。还测量了不良事件（AE）和严重不良事件（SAE）以及血糖/胰岛素水平。
在 3 个月和 6 个月时，治疗组之间的 ADAS-Cog13、CDR 总盒数（CDR-SOB）或 FAQ 评分无显著差异。与格鲁辛组相比，盐水组的受试者年龄明显更大（p=0.022）。治疗组之间在性别、教育程度、载脂蛋白 E4（ApoE4）状态和蒙特利尔认知评估（MoCA）评分方面无显著差异。总体而言，每组的不良事件人数相似（2.32 与 2.24；p=0.824），尽管接受鼻内格鲁辛的受试者鼻腔刺激（25.0% 与 13.9%）和呼吸道症状（15.9% 与 8.3%）的发生率高于安慰剂。治疗组和安慰剂组之间的血糖或低血糖发生率无差异。
鼻内格鲁辛相对安全且耐受性良好，并未持续影响外周血糖或胰岛素水平。鼻内格鲁辛对认知、功能或情绪没有增强作用，但由于成功入组的受试者数量和研究持续时间有限，检测显著性的能力受到限制。临床试验。
NCT02503501。
