Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome

Abstract Background Individuals with Down syndrome are likely to develop clinical and neuropathological brain changes resembling Alzheimer’s disease dementia by the ages of 35–40 years. Intranasal insulin is a potential treatment for neurodegenerative disease that has been shown to reduce amyloid pl...

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Main Authors: Michael Rosenbloom, Terry Barclay, Justin Johnsen, Lauren Erickson, Aleta Svitak, Maria Pyle, William Frey, Leah R. Hanson
Format: Article
Language:English
Published: Adis, Springer Healthcare 2020-02-01
Series:Drugs in R&D
Online Access:https://doi.org/10.1007/s40268-020-00296-2
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author Michael Rosenbloom
Terry Barclay
Justin Johnsen
Lauren Erickson
Aleta Svitak
Maria Pyle
William Frey
Leah R. Hanson
author_facet Michael Rosenbloom
Terry Barclay
Justin Johnsen
Lauren Erickson
Aleta Svitak
Maria Pyle
William Frey
Leah R. Hanson
author_sort Michael Rosenbloom
collection DOAJ
description Abstract Background Individuals with Down syndrome are likely to develop clinical and neuropathological brain changes resembling Alzheimer’s disease dementia by the ages of 35–40 years. Intranasal insulin is a potential treatment for neurodegenerative disease that has been shown to reduce amyloid plaque burden and improve verbal memory performance in normal as well as memory-impaired adults. Investigations have shown that rapid-acting insulins may result in superior cognitive benefits compared with regular insulin. Objectives The primary objective of this study was to measure the safety and feasibility of intranasal rapid-acting glulisine in subjects with Down syndrome. Secondarily, we estimated the effects of intranasal glulisine on cognition and memory in Down syndrome. Methods A single-center, single-dose, randomized, double-blind, placebo-controlled, cross-over pilot study was performed to test the safety of intranasal glulisine vs placebo in 12 subjects with Down syndrome aged ≥ 35 years. Intranasal administration utilized the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The primary outcomes were the occurrence of any or related adverse and serious adverse events. Secondary post-treatment cognitive outcome measures included performance on the Fuld Object-Memory Evaluation and Rivermead Behavioral Memory Test. Results Intranasal glulisine was safe and well tolerated in the Down syndrome population. No adverse or serious adverse events were observed. Conclusions Further investigations are necessary to better evaluate the potential cognitive-enhancing role of intranasal insulin in the Down syndrome population. ClinicalTrials.gov ID NCT02432716.
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spelling doaj.art-c289a4a0a4a04de79fa55f27ae5bd12b2022-12-21T17:22:11ZengAdis, Springer HealthcareDrugs in R&D1174-58861179-69012020-02-01201111510.1007/s40268-020-00296-2Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down SyndromeMichael Rosenbloom0Terry Barclay1Justin Johnsen2Lauren Erickson3Aleta Svitak4Maria Pyle5William Frey6Leah R. Hanson7HealthPartners Center for Memory and AgingHealthPartners Center for Memory and AgingHealthPartners Center for Memory and AgingHealthPartners InstituteHealthPartners Center for Memory and AgingHealthPartners Center for Memory and AgingHealthPartners Center for Memory and AgingHealthPartners Center for Memory and AgingAbstract Background Individuals with Down syndrome are likely to develop clinical and neuropathological brain changes resembling Alzheimer’s disease dementia by the ages of 35–40 years. Intranasal insulin is a potential treatment for neurodegenerative disease that has been shown to reduce amyloid plaque burden and improve verbal memory performance in normal as well as memory-impaired adults. Investigations have shown that rapid-acting insulins may result in superior cognitive benefits compared with regular insulin. Objectives The primary objective of this study was to measure the safety and feasibility of intranasal rapid-acting glulisine in subjects with Down syndrome. Secondarily, we estimated the effects of intranasal glulisine on cognition and memory in Down syndrome. Methods A single-center, single-dose, randomized, double-blind, placebo-controlled, cross-over pilot study was performed to test the safety of intranasal glulisine vs placebo in 12 subjects with Down syndrome aged ≥ 35 years. Intranasal administration utilized the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The primary outcomes were the occurrence of any or related adverse and serious adverse events. Secondary post-treatment cognitive outcome measures included performance on the Fuld Object-Memory Evaluation and Rivermead Behavioral Memory Test. Results Intranasal glulisine was safe and well tolerated in the Down syndrome population. No adverse or serious adverse events were observed. Conclusions Further investigations are necessary to better evaluate the potential cognitive-enhancing role of intranasal insulin in the Down syndrome population. ClinicalTrials.gov ID NCT02432716.https://doi.org/10.1007/s40268-020-00296-2
spellingShingle Michael Rosenbloom
Terry Barclay
Justin Johnsen
Lauren Erickson
Aleta Svitak
Maria Pyle
William Frey
Leah R. Hanson
Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome
Drugs in R&D
title Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome
title_full Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome
title_fullStr Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome
title_full_unstemmed Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome
title_short Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome
title_sort double blind placebo controlled pilot investigation of the safety of a single dose of rapid acting intranasal insulin in down syndrome
url https://doi.org/10.1007/s40268-020-00296-2
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