Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease

NCT ID: NCT02503501

Last Updated: 2020-04-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-28
• Study Completion Date: 2019-02-15

Brief Summary

This study evaluates the safety and effectiveness of intranasal (IN) glulisine in patients with amnestic mild cognitive impairment (aMCI) and probable Alzheimer's disease. Half of participants will receive IN glulisine, while the other half will receive IN placebo.

Detailed Description

Disruption of central nervous system (CNS) insulin signaling has been increasingly associated with Alzheimer's Disease pathogenesis, and consequently this disease has been referred to as a type III diabetes of the brain. Clinical trials of intranasal insulin in AD have demonstrated therapeutic effects of intranasal (IN) insulin in memory-impaired adults in terms of memory recall without significantly altering serum insulin or glucose levels. In this study, the investigators are investigating the chronic effects of the rapid acting insulin, glulisine, administered intranasally (IN) 20 IU two times daily in adults with amnestic-mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). The investigation will enroll n=90 subjects and follow them over a 6 month period.

This study has the following objectives:

1. Primary:

a. To measure the chronic effects of IN insulin glulisine on cognition and function in subjects with aMCI and probable mild AD over a 6 month period.

2. Secondary:

1. To measure the effect of IN insulin glulisine on mood in subjects with aMCI and mild AD over a 6 month period.

2. To measure the safety and efficacy of IN glulisine in aMCI and mild AD subjects with non-insulin dependent diabetes over a 6 month period.

3. Exploratory:

1. To measure the effect of IN delivery of insulin glulisine on parieto-temporal and posterior cingulate/precuneus glucose metabolism in subjects with aMCI and mild AD over a 6 month period.

2. To measure the chronic effect of IN delivery of insulin glulisine on AD-specific cerebrospinal (CSF) biomarkers (Abeta42, tau, and phospho-tau) in subjects with aMCI and mild AD over a 6 month period.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease (AD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Insulin Glulisine

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Group Type: EXPERIMENTAL

Insulin glulisine

Intervention Type: DRUG

Placebo

Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Bacteriostatic 0.9% Sodium Chloride

Interventions

Insulin glulisine

Intervention Type: DRUG

Placebo

Bacteriostatic 0.9% Sodium Chloride

Intervention Type: DRUG

Other Intervention Names

Apidra; Saline

Eligibility Criteria

Inclusion Criteria

Subject is/has

• clinical and research diagnosis of amnestic-MCI OR probable mild AD in accordance with National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
• Montreal Cognitive Assessment (MoCA) score 18-27
• Hachinski Ischemia Score <4
• 50-90 years of age
• Females at least 2 years post-menopausal or surgically sterile
• Proficiency in speaking, reading and understanding English
• Dedicated family member /caregiver, who will be able to attend all visits and report on subject's status
• (and family member/caregiver) provided fully informed written consent prior to participation. In the event that subject is legally unable to provide informed written consent due to deterioration in cognitive abilities, fully informed written consent must be provided by a legally authorized representative
• If AD, a brain computed tomography (CT) or magnetic resonance imaging (MRI) in the initial diagnostic workup or subsequent care that is compatible with the diagnosis of probable AD

Exclusion Criteria

Subject has/have/is

• medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including, but not limited to brain tumor, active subdural hematoma, seizure disorder, multiple sclerosis, dementia with Lewy bodies, vascular dementia, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease, multiple system atrophy, frontotemporal dementia, normal pressure hydrocephalus, Huntington's disease, or Jakob-Creutzfeldt disease presenting as dementia
• medical history and/or clinically determined disorders: current B12 deficiency, chronic sinusitis, any untreated thyroid disease, significant head trauma and history of difficulty with smell and/or taste prior to AD diagnosis
• history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, condition known to affect absorption, distribution, metabolism, or excretion of drugs such as any hepatic, renal or gastrointestinal disease or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator
• previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies
• history of any psychiatric illness, with the exception of major depressive and anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, version 5, Text Revision (DSM-IV TR)) currently in remission or stable with treatment for > 2 yrs, or any other psychiatric condition that inclusion would pose a safety risk to the subject as determined by investigator
• currently taking any medications, herbals and food supplements that are medically/clinically contraindicated as determined by investigator in order to comply with procedural testing of cognitive function as well as ensure study safety. See list of prohibited medications and compounds
• undergone a recent change (<1mo) in their prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) or memantine.
• undergone a recent change (<1mo) in their selective serotonin re-uptake inhibitor (SSRI) or anti-depressant medication
• current or recent drug or alcohol abuse or dependence as defined by DSM-IV TR
• laboratory results that are medically relevant, in which inclusion would pose a safety risk to the subject as determined by investigator
• participated in any other research study at least 3 mos prior to this study
• an insulin allergy

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HealthPartners Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael H Rosenbloom, MD

Role: PRINCIPAL_INVESTIGATOR

HealthPartners Institute

Locations

HealthPartners Riverside

Minneapolis, Minnesota, United States

HealthPartners Neuroscience Center

Saint Paul, Minnesota, United States

Countries

United States

References

Rosenbloom M, Barclay TR, Kashyap B, Hage L, O'Keefe LR, Svitak A, Pyle M, Frey W, Hanson LR. A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease. Drugs Aging. 2021 May;38(5):407-415. doi: 10.1007/s40266-021-00845-7. Epub 2021 Mar 15.

Reference Type: DERIVED

PMID: 33719017 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.healthpartners.com/memoryloss

HealthPartners Center for Memory and Aging

Other Identifiers

IN-INSUL-MCI-AD

Identifier Type: -

Identifier Source: org_study_id