To determine the safety and tolerability of three doses of intranasal (IN) insulin in patients with Parkinson’s disease (PD)

A promising new strategy for the treatment of neurodegenerative disorders is the repurposing of therapeutic treatments for diabetes.  IN insulin is one such treatment that has been shown to improve memory, attention, and cognition in Alzheimer’s dementia. Due to associations between PD etiology and central insulin resistance, IN insulin may be a promising treatment for PD.

A phase II single center, randomized, double-blind clinical trial was conducted in subjects with PD, aged 41-89, MoCA ≥ 16, and on stable antiparkinsonian medications. Subjects received intranasal treatment for 21 days with normal saline, 20, 40, or 80 IU of Novolin R. Safety and tolerability were assessed by measuring hypoglycemia, weight, and adverse events. Cognitive, mood, and motor measures were collected pre- and post-treatment.

Of the 31 subjects enrolled, 28 completed the study, with 2 screen fails and 1 withdrawal. Overall, there was no significant change in weight or insulin levels post-treatment. No hypoglycemia (<70mg/dl) was noted 15 or 30 minutes post-dose. After post-hoc adjustment, the 40 IU and 80 IU dose groups showed marginally significant (but not clinically relevant) declines in glucose levels, but not the placebo or 20 IU dose groups. The average per person adverse event rate was similar in the placebo and 20 IU groups (3.0 and 2.8), and 35-67% higher in the 80 and 40 IU groups (3.8 and 5.0). Most adverse events were mild and related to nasal irritation.

IN insulin exhibits an acceptable safety profile in patients with PD. This is one of the first explorations into safety of IN insulin in PD. Further testing is warranted to determine whether it is efficacious in reducing motor and cognitive symptoms in this population.