Safety and Preliminary Efficacy of Intranasal Insulin for Cognitive Impairment in Parkinson Disease and Multiple System Atrophy

A double-blinded placebo-controlled pilot study in parkinson disease and
multiple system atrophy.

Parkinson disease (PD) is associated with cognitive impairment. We aimed to
determine the effects of intranasal insulin (INI) on cognition and motor
performance in PD. This was a proof of concept, randomized, double-blinded,
placebo-controlled trial evaluating the effects of 40 international units (IU)
of insulin or saline once daily for four weeks on cognitive and functional
performance. Of 16 subjects enrolled, eight in the INI group and six in the
placebo group completed verbal fluency (FAS), Unified Parkinson Disease Scale
(UPDRS), and modified Hoehn and Yahr scale (HY, PD severity) at baseline and
post-treatment and were included in the analyses. After treatment, the INI
group had a better total FAS score (p=0.02) (41 ± 8.2 vs. 30.8 ± 7.1, mean ±SD
_,_ __ p=0.02) compared to the placebo group. The INI group also had improved
HY (p=0.04) and UPDRS-Motor (Part III) (p=0.02) scores when compared to
baseline. One INI treated patient with multiple system atrophy (MSA) remained
stable and did not show disease progression. The placebo group had no change.
INI administration was well tolerated and there were no hypoglycemic episodes
or serious study related adverse events or medications interactions.

INI is safe in PD and MSA patients and may provide clinically relevant
functional improvement. Larger studies are warranted to determine the INI
effect in treatment of cognitive and motor impairment in Parkinson disease.
NCT02064166.

一项针对帕金森病（Parkinson Disease, PD）与多系统萎缩的双盲安慰剂对照预试验。
帕金森病常伴随认知功能损害。本研究旨在探究鼻内胰岛素（Intranasal Insulin, INI）对帕金森病患者认知与运动功能的影响。本试验为概念验证性随机双盲安慰剂对照研究，评估每日单次给予40国际单位（IU）胰岛素或生理盐水、持续4周，对受试者认知与功能状态的影响。本研究共纳入16名受试者，其中鼻内胰岛素组8人、安慰剂组6人完成了基线与治疗后的语言流畅性（FAS）、统一帕金森病评定量表（Unified Parkinson Disease Scale, UPDRS）以及改良Hoehn-Yahr量表（HY，PD病情严重程度评估）测评，并纳入最终分析。治疗结束后，与安慰剂组相比，鼻内胰岛素组的FAS总分更高（P=0.02，均值±标准差：41±8.2 vs 30.8±7.1）。相较于基线水平，鼻内胰岛素组的HY评分（P=0.04）与UPDRS运动部分（第三部分）评分（P=0.02）均得到改善。1名接受鼻内胰岛素治疗且合并多系统萎缩（Multiple System Atrophy, MSA）的患者病情保持稳定，未出现疾病进展；安慰剂组则无此类变化。鼻内胰岛素给药耐受性良好，未出现低血糖事件、严重研究相关不良事件或药物相互作用。
鼻内胰岛素在帕金森病与多系统萎缩患者中具有安全性，或可带来具有临床意义的功能改善。未来需开展更大规模的研究，以明确鼻内胰岛素用于改善帕金森病患者认知与运动功能损害的疗效。本试验注册号为NCT02064166。