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CompletedPhase 2Results posted

SNIFF - Combo INI+EMPA Trial

Study of Nasal Insulin to Fight Forgetfulness - Combination Intranasal Insulin and Empagliflozin Trial

Assets

Empagliflozin / Insulin

Listed sites

1

Recruiting sites

-

Enrollment

47

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

Alzheimer's diseaseAmyloid biomarker required (PET/CSF)

Primary endpoint

Treatment-Related Serious Adverse Events

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 IDIRB00075245
NCT IDNCT05081219

Timeline

Milestones

Study start2021-09-14actual
Study first posted2021-10-18actual
Primary completion2024-09-17actual
Study completion2024-09-17actual
Last update posted2025-10-21actual
Results first posted2025-10-21actual

Assets

Drug assets

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age55 Years
Maximum age85 Years
SexAll
Healthy volunteersAccepted

Inclusion criteria

1. Age 55 to 85 (inclusive)

2. Fluent in English

3. Cognitively normal or diagnosis of amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD)

4. Amyloid positive by positron emission tomography (PET) or cerebrospinal fluid (CSF) criteria

5. Stable medical condition for 3 months prior to screening visit

6. Stable medications for 4 weeks prior to the screening and study visits (exceptions may be made on a case by case basis by the study physician)

7. Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician

Exclusion criteria

1. A diagnosis of dementia other than Alzheimer's disease (AD)

2. History of a clinically significant stroke

3. Current evidence or history in past two years of epilepsy, head injury with loss of consciousness, any major psychiatric disorder including psychosis, major depression, bipolar disorder

4. Diabetes (type I or type II) insulin-dependent and non-insulin-dependent diabetes mellitus

5. Current or past regular use of insulin or any other anti-diabetic medication within 2 months of screening visit

6. History of seizure within past five years

7. Pregnancy or possible pregnancy

8. Use of anticoagulants, unless documentation received from prescribing clinician that anticoagulant medication can be held before lumbar puncture, and approved by study clinician

9. Residence in a skilled nursing facility at screening

10. Use of an investigational agent within two months of screening visit

11. Regular use of alcohol, narcotics, anticonvulsants, anti-parkinsonian medications, or any other exclusionary medications (exceptions may be made on a case by case basis by the study physician)

Endpoints (16)

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
Amyloid biomarkers
4
Tau biomarkers
2
Neuroimaging
2
Fluid / digital biomarkers
2
Safety / tolerability / PK
2

Global cognition

4 endpoints
Secondary/protocol endpoint

Change in the Preclinical Alzheimer Cognitive Composite V5 (PACC5) Z-Score

Time frame:Baseline to Week 4

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score

Time frame:Baseline to Week 4

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change in the Preclinical Alzheimer Cognitive Composite V5 (PACC5) Z-Score

Time frame:Baseline to Week 4

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

GroupValue (mean), z-scoreStandard deviation
Intranasal Insulin and Empagliflozin Placebon=9 Participants0.20.1
Empagliflozin and Intranasal Insulin Placebon=12 Participants0.00.2
Intranasal Insulin and Empagliflozinn=11 Participants0.20.2
Placebon=8 Participants-0.10.4
Secondary/registry result

Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score

Time frame:Baseline to Week 4

ADAS-Cog

change from baseline, improvement

Posted result

GroupValue (mean), score on a scaleStandard deviation
Intranasal Insulin and Empagliflozin Placebon=9 Participants-0.54.0
Empagliflozin and Intranasal Insulin Placebon=12 Participants1.03.5
Intranasal Insulin and Empagliflozinn=11 Participants2.04.0
Placebon=8 Participants1.24.6

Amyloid biomarkers

4 endpoints
Secondary/protocol endpoint

Change in Amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/protocol endpoint

Change in Amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result

Change in Amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

GroupValue (mean), pg/mlStandard deviation
Intranasal Insulin and Empagliflozin Placebon=10 Participants10.61667.4
Empagliflozin and Intranasal Insulin Placebon=12 Participants-417.2822.8
Intranasal Insulin and Empagliflozinn=8 Participants-159.6396.8
Placebon=9 Participants-223.61025.3
Secondary/registry result

Change in Amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

GroupValue (mean), pg/mlStandard deviation
Intranasal Insulin and Empagliflozin Placebon=10 Participants-29.9169.6
Empagliflozin and Intranasal Insulin Placebon=12 Participants-40.697.0
Intranasal Insulin and Empagliflozinn=8 Participants-26.643.0
Placebon=9 Participants-5.1102.4

Tau biomarkers

2 endpoints
Secondary/protocol endpoint

Change in Cerebrospinal Fluid (CSF) Levels of Total Tau

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result

Change in Cerebrospinal Fluid (CSF) Levels of Total Tau

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

GroupValue (mean), pg/mlStandard deviation
Intranasal Insulin and Empagliflozin Placebon=10 Participants2.652.3
Empagliflozin and Intranasal Insulin Placebon=12 Participants-20.136.4
Intranasal Insulin and Empagliflozinn=8 Participants-2.624.4
Placebon=9 Participants7.733.6

Neuroimaging

2 endpoints
Secondary/protocol endpoint

Change in Total Cerebral Blood Flow (CBF) Using MRI Pseudocontinuous Arterial Spin Labeling (ASL)

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result

Change in Total Cerebral Blood Flow (CBF) Using MRI Pseudocontinuous Arterial Spin Labeling (ASL)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

GroupValue (mean), mL/100g/minStandard deviation
Intranasal Insulin and Empagliflozin Placebon=9 Participants-0.45.4
Empagliflozin and Intranasal Insulin Placebon=11 Participants-1.85.4
Intranasal Insulin and Empagliflozinn=10 Participants-0.52.8
Placebon=8 Participants3.94.5

Fluid / digital biomarkers

2 endpoints
Secondary/protocol endpoint

Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result

Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

GroupValue (mean), pg/mlStandard deviation
Intranasal Insulin and Empagliflozin Placebon=10 Participants1.07.1
Empagliflozin and Intranasal Insulin Placebon=12 Participants-1.93.8
Intranasal Insulin and Empagliflozinn=8 Participants0.35.5
Placebon=9 Participants0.53.4

Safety / tolerability / PK

2 endpoints
Primary/protocol endpoint

Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0

Time frame:Week 8

event count, event

Primary/registry result

Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0

Time frame:Week 8

event count, event

Posted result

GroupValue (number), participantsReported bounds
Intranasal Insulin and Empagliflozin Placebon=13 Participants0-
Empagliflozin and Intranasal Insulin Placebon=12 Participants0-
Intranasal Insulin and Empagliflozinn=11 Participants0-
Placebon=10 Participants0-

Publications (53)

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.