CompletedPhase 2Results posted

Safety and Effectiveness Study of Intranasal Insulin Glulisine on Cognitive and Memory in Mild-Mod AD Patients.

A Double-Blind, Placebo-Controlled Single Dose Study of the Safety and Efficacy of Glulisine on Cognitive Function and Memory in Individuals Diagnosed With Probable Mild to Moderate Alzheimer's Disease/Intranasal Insulin Study.

Lead sponsor

HealthPartners Institute

Asset

Insulin glulisine

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 18-26•Study partner/caregiver required•AD symptomatic therapy: stable ≥1 months

Primary endpoints

•Cognitive Performance•Trails B - Seconds•Trails B - Errors

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID11-111

NCT IDNCT01436045

Timeline

Milestones

Study start2011-09 (month precision)

Study first posted2011-09-19estimated

Primary completion2013-06actual (month precision)

Study completion2013-06actual (month precision)

Last update posted2015-10-19estimated

Results first posted2015-10-19estimated

Assets

Drug assets

Insulin glulisine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age65 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male or female subject with a clinical diagnosis of probable 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 and Dementia Rating Scale (McKhann 1984).

•Mini-Mental State Examination (MMSE) score of 18-26.

•Hachinski Ischemia Score < 4.

•Age is > 65 and <85 years

•Females must be > 2 years post-menopausal or surgically sterile.

•Must be able to speak, read and understand English in order to comply with testing of cognitive function, memory and physiology.

•Must have a dedicated family member /caregiver, able to attend all visits and report on subject's status.

•Subject and family member/caregiver have both 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.

•On a stable dose (≥ 1 months) of a prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) and/or memantine.

•A brain CT or MRI in the last 2 years compatible with the diagnosis of probable Alzheimer's Disease.

•A Clinical Dementia Rating (CDR) ranging from 1 to 2

Exclusion criteria

•Medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including 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.

•Personal medical history and/or clinically determined disorders: current B12 deficiency, positive syphilis serology, chronic sinusitis or any untreated thyroid disease, significant head trauma, or history of difficulty with smell and/or taste prior to AD diagnosis.

•Diagnosis with any form of diabetes mellitus, actively takes insulin, or has HbA1c > 6.1 % at screening.

•Personal history of any of the following: moderate to severe pulmonary disease, congestive heart failure, significant cardiovascular and/or cerebrovascular events in 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.

•Heavy smoker (defined as smoking half a pack or more per day in the last 10 years prior to entry in the study).

•Personal history of any psychiatric illness, except major depressive disorder (according to Diagnostic and Statistical Manual (DSM)-IV TR) currently in remission or stable with treatment for > 2 years, or any other psychiatric condition that inclusion would pose a safety risk to the subject as determined by Investigator. Patients with active depression (Geriatric Depression Score>9) are excluded from the study.

•Currently taking any medications, herbals and food supplements that are determined by Investigator to interfere with procedural testing of cognitive function as well as ensure study safety.

•Recent change (< 1 months) in prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) or memantine.

•Current or recent drug or alcohol abuse or dependence defined by DSM-IV TR.

•Systolic blood pressure > 160 or < 90 mmHg or diastolic blood pressure > 100 or < 60 mmHg at Screening.

•Screening laboratory results that are medically relevant and which would pose a safety risk to the subject as determined by Investigator.

•Participation in any other research study at least 3 months prior to this study.

•Insulin allergy.

•History of significant traumatic brain injury

•History of acute and chronic rhinitis and/or sinusitis.

•Legally unable to provide informed written consent due to deterioration in cognitive abilities.

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Global cognition

Memory

Global cognition

2 endpoints

Primary/protocol endpoint

Cognitive Performance

Time frame:20 minutes post-intranasal administration

event count, event

Primary/registry result

Cognitive Performance

Time frame:20 minutes post-intranasal administration

event count, event

Posted result

Group	Value (mean), mean total correct responses	Standard error
Post-Insulin GlulisineRBANS List Learningn=12 Participants	15.92	1.32
RBANS Story Memoryn=12 Participants	8.58	1.17
RBANS Figure Copyn=12 Participants	16.58	0.98
RBANS Line Orientationn=12 Participants	14.25	0.97
RBANS Semantic Fluencyn=12 Participants	12.25	1.38
RBANS List Recalln=12 Participants	0.83	0.42
RBANS List Recognitionn=12 Participants	14.92	0.69
RBANS Story Recalln=12 Participants	2.12	0.96
RBANS Figure Recalln=12 Participants	4.83	1.84
Digit Span Forwardn=12 Participants	9.42	0.50
Digit Span Backwardn=12 Participants	5.58	0.45
Boston Naming Testn=12 Participants	11.75	1.05
Post-PlaceboRBANS List Learningn=12 Participants	16.67	2.02
RBANS Story Memoryn=12 Participants	8.41	1.55
RBANS Figure Copyn=12 Participants	16.92	3.42
RBANS Line Orientationn=12 Participants	12.25	1.38
RBANS Semantic Fluencyn=12 Participants	12.5	1.75
RBANS List Recalln=12 Participants	1.0	0.51
RBANS List Recognitionn=12 Participants	14.75	0.97
RBANS Story Recalln=12 Participants	2.33	0.90
RBANS Figure Recalln=12 Participants	4.92	1.59
Digit Span Forwardn=12 Participants	9.0	0.44
Digit Span Backwardn=12 Participants	5.75	0.49
Boston Naming Testn=12 Participants	11.75	1.10

Percent Change-15.7p<0.05t-test, 2 sided

Response to intranasal Insulin Gluiline \[(result post-insulin - result post-placebo)/(result post-placebo)\] x 100%

Memory

2 endpoints

Secondary/protocol endpoint

Olfactory Function

Time frame:60 minute post intranasal administration

ratio, descriptive

Secondary/registry result

Olfactory Function

Time frame:60 minute post intranasal administration

ratio, descriptive

Posted result

Group	Value (mean), ratio of area under the sniff curve	Standard error
Post-Insulin Glulisinen=12 Participants	2.5	0.15
Post Placebon=12 Participants	2.33	0.19

Other (unclassified)

4 endpoints

Primary/protocol endpoint/low confidence

Trails B - Seconds

Time frame:20 minutes post-intranasal administration

event count, event

Primary/protocol endpoint/low confidence

Trails B - Errors

Time frame:20 minutes post-intranasal administration

event count, event

Primary/registry result/low confidence

Trails B - Seconds

Time frame:20 minutes post-intranasal administration

event count, event

Posted result

Group	Value (mean), mean seconds	Standard error
Post-Insulin Glulisinen=12 Participants	166.83	20.82
Post-Placebon=12 Participants	177.25	21.65

Primary/registry result/low confidence

Trails B - Errors

Time frame:20 minutes post-intranasal administration

event count, event

Posted result

Group	Value (mean), mean number of errors	Standard error
Post-Insulin Glulisinen=12 Participants	1.17	0.27
Post-Placebon=12 Participants	2.08	0.31

Mean Difference (Final Values)0.92p<0.05t-test, 2 sided

Difference in errors \[result post-insulin - result post-placebo\]

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.