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

• Published in: Contemporary clinical trials 2020-02, Vol.89, p.105934-105934, Article 105934
• Main Authors: Galindo-Mendez, B., Trevino, J.A., McGlinchey, R., Fortier, C., Lioutas, V., Novak, P., Mantzoros, C.S., Ngo, L., Novak, V.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Aged; Aged, 80 and over; Balance; Cognition; Cognition - drug effects; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - etiology; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; Female; Functionality; Gait; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Insulin - administration & dosage; Insulin - therapeutic use; Intranasal insulin; Longitudinal Studies; Male; Memory; Memory - drug effects; Middle Aged; Multicenter Studies as Topic; Physical Functional Performance; Prospective Studies; Randomized controlled clinical trial; Randomized Controlled Trials as Topic; Research Design; Type 2 diabetes mellitus; Walking Speed
• ISSN: 1551-7144; 1559-2030
• DOI: 10.1016/j.cct.2020.105934

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. 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. 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