Pilot Randomized, Double-Blind, Placebo-Controlled Crossover Trial Evaluating the Feasibility of an Intranasal Oxytocin in Improving Social Cognition in Individuals Living with Alzheimer’s Disease

Abstract

Background: Individuals living with Alzheimer’s disease (AD) demonstrate extensive deficits in social cognition. To date, no studies have investigated the feasibility of an intranasal oxytocin (INOT) treatment to improve social cognition in individuals living with AD. Objective: We conducted a pilot trial to determine recruitment feasibility, enrolment acceptability, and adherence to an INOT treatment to inform on the subsequent design of a future randomized controlled trial (RCT). We also estimated the effect sizes of potential social cognitive function outcome measures related to participants and their caregivers. Methods: Four individuals with AD were enrolled in a single-center, randomized, double-blind, placebo-controlled crossover trial involving a one-week treatment period with both INOT (72 IU twice-daily) and placebo. Results: All participants reported no treatment-causative or serious adverse events following repeated INOT administration. While enrolment acceptability (100%) and INOT adherence (placebo, 95%; INOT, 98%) were excellent, feasibility of recruitment was not acceptable (i.e., n = 4/58 individuals screened met inclusion criteria). However, positive/large effects were associated with secondary outcomes of self-reported health and wellbeing, caregiver ‘burden’, intimacy and interpersonal-bonding, following repeated INOT administration. No positive effects were associated with participant outcomes of social cognition. Conclusion: This pilot RCT provides first evidence that INOT administration in individuals living with AD is safe and well-tolerated. Despite limitations in sample size, moderate-to-large effect size improvements were identified in participant health outcomes as well as core social cognitive functions and ‘burden’ as reported by a caregiver. This suggests potential broad-ranging beneficial effects of INOT which should be assessed in future RCTs.

Research progress in brain-targeted nasal drug delivery

“…Alzheimer's disease Insulin (Larijani et al, 2023), Oxytocin (Michaelian et al, 2023), Resveratrol (Fonseca-Santos et al, 2023), etc.…”