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

NCT02503501 | Terminated Phase 2 Results DMC

• 1 other identifier: IN-INSUL-MCI-AD
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

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.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease (AD)

Keywords

Memory; Insulin glulisine; Alzheimer's disease; Mild Cognitive Impairment; Intranasal insulin; Cognition Disorders

Outcome Measures

Primary Outcomes (3)

• Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)

  The ADAS-Cog was developed as an outcome measure for global cognition in clinical trials for Alzheimer's disease. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. The modified ADAS-Cog 13-item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a total of 85 points (0: no cognitive impairment; 85: severe impairment).

  Baseline and 6 months

• Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale

  The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). The total CDR ratings for each of the six cognitive/functional domains can be added to create a CDR sum of boxes (SOB). The overall SOB score ranges from 0 to 18; with 18 indicating severe impairment and 0 indicating no impairment.

  Baseline and 6 months

• Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)

  The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The FAQ is a sum of scores ranging from 0 (normal) to 30 (complete dependence on others).

  Baseline and 6 months

Study Arms (2)

Insulin Glulisine

EXPERIMENTAL

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

Drug: Insulin glulisine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Insulin glulisine DRUG

Also known as: Apidra

Insulin Glulisine

Placebo DRUG

Bacteriostatic 0.9% Sodium Chloride

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies
• 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
• participated in any other research study at least 3 mos prior to this study
• an insulin allergy

Sponsors & Collaborators

• HealthPartners Institute: lead

Study Sites (2)

HealthPartners Riverside

Minneapolis, Minnesota, 55455, United States

Location

HealthPartners Neuroscience Center

Saint Paul, Minnesota, 55130, United States

Location

Related Publications (1)

• 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.

  PMID: 33719017 DERIVED

Related Links

• HealthPartners Center for Memory and Aging

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Cognition Disorders

Interventions

insulin glulisine; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Clinical Research Manager
• Organization: HealthPartners Neuroscience Research

aleta.l.svitak@healthpartners.com

651-495-6363

Study Officials

• Michael H Rosenbloom, MD

  HealthPartners Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 21, 2015
• Study Start: September 28, 2015
• Primary Completion: February 11, 2019
• Study Completion: February 15, 2019
• Last Updated: April 9, 2020
• Results First Posted: April 9, 2020

Record last verified: 2020-01

Locations

US (2)