Memory advancement by intranasal insulin in type 2 diabetes (MemAID) randomized controlled clinical trial: Design, methods and rationale

Abstract

Background: Type 2 diabetes mellitus (T2DM) accelerates brain aging and increases the risk for dementia. Insulin is a key neurotrophic factor in the brain, where it modulates energy metabolism, neurovascular coupling, and regeneration. Impaired insulin-mediated brain signaling and central insulin resistance may contribute to cognitive and functional decline in T2DM. Intranasal insulin (INI) has emerged as a potential therapy for treating T2DM-related cognitive impairment.

Methods/design: Ongoing from 2015, a prospective, two-center, randomized, double-blind, placebo-controlled trial of 210 subjects (120 T2DM and 90 non-diabetic older adults) randomized into four treatment arms (60 T2DM-INI, 60 T2DM-Placebo, 45 Control-INI, and 45 Control-Placebo) evaluating the long-term effects of daily intranasal administration of 40 International Units (IU) of human insulin, as compared to placebo (sterile saline) over 24 weeks and 24 weeks of post-treatment follow-up. Study outcomes are: 1) long-term INI effects on cognition, daily functionality, and gait speed; 2) identifying a clinically relevant phenotype that predicts response to INI therapy; 3) long-term safety.

Conclusion: This study addresses an important knowledge gap about the long-term effects of intranasal insulin on memory and cognition in older people with T2DM and non-diabetic controls, and may provide a novel therapeutic target for prevention and treatment of cognitive and functional decline and dementia. Trial Registration NCT02415556.

Keywords: Balance; Cognition; Functionality; Gait; Intranasal insulin; Memory; Randomized controlled clinical trial; Type 2 diabetes mellitus.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1:. Study roadmap and interventions

After completing phone screening, subjects complete on-site screening. Intervention period visits happen every four weeks; follow-up period visits happen every eight weeks. V2 includes two assessments: baseline and intervention. Visit 9 is a phone call. Abbreviations: V, Visit number; MMSE: Mini Mental State Examination; WHODAS 2.0: World Health Organization Disability Assessment Scale; GDS: Geriatric Depression Scale; AE: Adverse Event; INI: intranasal insulin. See text for more details.