B Galindo-Mendez1, J A Trevino1, R McGlinchey2, C Fortier2, V Lioutas1, P Novak3, C S Mantzoros4, L Ngo5, V Novak6. 1. Department of Neurology, SAFE Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 2. Translational Research Center for TBI and Stress Disorders (TRACTS), Geriatric Research Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 3. Autonomic Laboratory, Department of Neurology, Brigham and Women's Faulkner Hospital, Harvard Medical School, Boston, MA, USA. 4. Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA; Department of Medicine, Boston VA Healthcare System, Harvard Medical School, Boston, MA. 5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. Department of Neurology, SAFE Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: vnovak@bidmc.harvard.edu.
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.
RCT Entities:
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 humaninsulin, 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.
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