The Study of Nasal Insulin in the Fight Against Forgetfulness (SNIFF) - Alzheimer’s Disease & Related Dementias Atlas

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 IDADC-046-INI

NCT IDNCT01767909

NihRF1AG041845

Timeline

Milestones

Study first posted2013-01-15estimated

Study start2014-01-08actual

Primary completion2018-12-11actual

Study completion2018-12-11actual

Results first posted2020-05-18actual

Last update posted2024-11-20actual

Assets

Drug assets

Insulin

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Fluent in English or Spanish

•Diagnosis of aMCI by Petersen criteria or probable AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria

•Mini Mental State Examination (MMSE) score at screening is greater than or equal to 20

•Clinical Dementia Rating is 0.5-1 at screening

•Logical Memory is less than or equal to 8 for 16 or more years of education, less than or equal to 4 for 8-15 years of education, less than or equal to 2 for 0-7 years of education. Scores measured at screening on Delayed Paragraph Recall (Paragraph A only) from the Wechsler Memory Scale-Revised

•Able to complete baseline assessments

•Modified Hachinski score of less than or equal to 4

•A study partner able to accompany the participant to most visits and answer questions about the participant

•The study partner must have direct contact with the participant more than 2 days per week (minimum of 10 hours per week) and provide supervision of drug administration as needed

•Stable medical condition for 3 months prior to screening visit

•Stable medications for 4 weeks prior to the screening and baseline visits

•Stable use of permitted medications

•At least six years of education or work history

•Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator

•Visual and auditory acuity adequate for neuropsychological testing

Exclusion criteria

•A diagnosis of dementia other than probable AD

•Probable AD with Down syndrome

•History of clinically significant stroke

•Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse

•Sensory impairment that would preclude the participant from participating in or cooperating with the protocol

•Diabetes (type 1 or type II) requiring pharmacologic treatment (including both insulin dependent and non-insulin dependent diabetes mellitus)

•Current or past use of insulin or any other anti-diabetic medication

•Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.

•Active neoplastic disease, history of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not excluded)

•History of seizure within the past five years

•Pregnancy or possible pregnancy

•Contraindications to Lumbar Puncture (LP) procedure: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets is less than 100,000 or history of bleeding disorder

•Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa) due to LP requirement

•Contraindications for MRI (claustrophobia, craniofacial metal implants of any kind, pacemakers)

•Residence in a skilled nursing facility at screening

•Use of an investigational agent within two months or screening visit

•Regular use of narcotics, anticonvulsants, medications with significant anticholinergic activity, antiparkinsonian medications or any other exclusionary medications

Endpoints (12)

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

Global cognition

4

Memory

2

Function / daily living

2

Amyloid biomarkers

2

Neuroimaging

2

Global cognition

4 endpoints

Primary/protocol endpoint

Change in Global Measure of Cognition as Measured by the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12)

Time frame:12 months (blinded phase) followed by 6 months (open label phase)

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change in Global Measure of Cognition as Measured by the Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12)

Time frame:12 months (blinded phase) followed by 6 months (open label phase)

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Modeled change score on a scale	Standard error
Insulin (Humulin® R U-100)Blinded Phase (M12 change from Baseline)n=121 Participants	3.893	0.643
Open Label Phase (M18 change from Baseline)n=121 Participants	7.091	0.937
PlaceboBlinded Phase (M12 change from Baseline)n=119 Participants	3.867	0.650
Open Label Phase (M18 change from Baseline)n=119 Participants	6.164	0.942

Secondary/protocol endpoint

Change in Cognitive Deficit as Measured by Clinical Dementia Rating - Sum of Boxes (CDR-SB)

Time frame:12 months (blinded phase) followed by 6 months (open label phase)

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/registry result

Change in Cognitive Deficit as Measured by Clinical Dementia Rating - Sum of Boxes (CDR-SB)

Time frame:12 months (blinded phase) followed by 6 months (open label phase)

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Modeled change in test score	Standard error
Insulin (Humulin® R U-100)Blinded Phase (M12 change from Baseline)n=121 Participants	1.682	0.195
Open Label Phase (M18 change from Baseline)n=121 Participants	2.361	0.247
PlaceboBlinded Phase (M12 change from Baseline)n=119 Participants	1.402	0.196
Open Label Phase (M18 change from Baseline)n=119 Participants	2.122	0.249

Memory

2 endpoints

Secondary/protocol endpoint

Change in Memory Composite as Measured by Story Recall (Immediate Paragraph Recall and Delayed Paragraph Recall) and Free and Cued Selective Reminding Test (FCSRT)

Time frame:12 months (blinded phase) followed by 6 months (open label phase)

change from baseline, improvement

Secondary/registry result

Change in Memory Composite as Measured by Story Recall (Immediate Paragraph Recall and Delayed Paragraph Recall) and Free and Cued Selective Reminding Test (FCSRT)

Time frame:12 months (blinded phase) followed by 6 months (open label phase)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), modeled change score on a scale	Standard error
Insulin (Humulin® R U-100)Blinded Phase (M12 change from Baseline)n=121 Participants	-0.496	0.163
Open Label Phase (M18 change from Baseline)n=121 Participants	-0.594	0.183
PlaceboBlinded Phase (M12 change from Baseline)n=119 Participants	-0.433	0.162
Open Label Phase (M18 change from Baseline)n=119 Participants	-0.802	0.184

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change in Daily Functioning as Measured by the ADCS-MCI Activities of Daily Living (ADCS-ADL-MCI)

Time frame:12 months (blinded phase) and 6 months (open label phase)

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change in Daily Functioning as Measured by the ADCS-MCI Activities of Daily Living (ADCS-ADL-MCI)

Time frame:12 months (blinded phase) and 6 months (open label phase)

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), modeled change score on a scale	Standard error
Insulin (Humulin® R U-100)Blinded Phase (M12 change from Baseline)n=121 Participants	-3.63	0.769
Open Label Phase (M18 change from baseline)n=121 Participants	-7.35	0.925
PlaceboBlinded Phase (M12 change from Baseline)n=119 Participants	-4.26	0.779
Open Label Phase (M18 change from baseline)n=119 Participants	-6.56	0.934

Amyloid biomarkers

2 endpoints

Secondary/protocol endpoint

Change in CSF Biomarkers of AD

Time frame:Baseline and Month 12

change from baseline, improvement

Secondary/registry result

Change in CSF Biomarkers of AD

Time frame:Baseline and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), pg/ml	Standard deviation
Insulin (Humulin® R U-100)Abeta 40n=72 Participants	-264.851	1168.995
Abeta 42n=72 Participants	-15.552	61.884
Total Taun=72 Participants	-4.717	263.810
p-Taun=72 Participants	-2.764	18.729
PlaceboAbeta 40n=75 Participants	-127.539	1600.604
Abeta 42n=75 Participants	-4.456	82.156
Total Taun=75 Participants	1.937	291.160
p-Taun=75 Participants	-0.567	25.293

Neuroimaging

2 endpoints

Secondary/protocol endpoint

Change in Hippocampal and Entorhinal Atrophy as Measured by Magnetic Resonance Imaging (MRI)

Time frame:Screen and Month 12

change from baseline, improvement

Secondary/registry result

Change in Hippocampal and Entorhinal Atrophy as Measured by Magnetic Resonance Imaging (MRI)

Time frame:Screen and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), % change in volume	Standard deviation
Insulin (Humulin® R U-100)Normalized hippocampal volume changen=116 Participants	-0.01	0.02
Normalized entorhinal volume changen=116 Participants	-0.01	0.03
Normalized whole brain volume changen=116 Participants	-1.35	1.09
PlaceboNormalized hippocampal volume changen=116 Participants	-0.02	0.02
Normalized entorhinal volume changen=116 Participants	-0.01	0.03
Normalized whole brain volume changen=116 Participants	-1.41	1.18

Publications (7)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.