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SNIFF - Combo INI+EMPA Trial
Study of Nasal Insulin to Fight Forgetfulness - Combination Intranasal Insulin and Empagliflozin Trial
Lead sponsor
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 disease•Amyloid 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
Timeline
Milestones
Assets
Drug assets
Study populations
Who this study enrolls
Eligibility
Who can enroll
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 endpointsChange 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
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
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
| Group | Value (mean), z-score | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=9 Participants | 0.2 | 0.1 |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | 0.0 | 0.2 |
| Intranasal Insulin and Empagliflozinn=11 Participants | 0.2 | 0.2 |
| Placebon=8 Participants | -0.1 | 0.4 |
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
| Group | Value (mean), score on a scale | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=9 Participants | -0.5 | 4.0 |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | 1.0 | 3.5 |
| Intranasal Insulin and Empagliflozinn=11 Participants | 2.0 | 4.0 |
| Placebon=8 Participants | 1.2 | 4.6 |
Amyloid biomarkers
4 endpointsChange in Amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)
Time frame:Baseline to Week 4
change from baseline, improvement
Change in Amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)
Time frame:Baseline to Week 4
change from baseline, improvement
Change in Amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)
Time frame:Baseline to Week 4
change from baseline, improvement
Posted result
| Group | Value (mean), pg/ml | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=10 Participants | 10.6 | 1667.4 |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | -417.2 | 822.8 |
| Intranasal Insulin and Empagliflozinn=8 Participants | -159.6 | 396.8 |
| Placebon=9 Participants | -223.6 | 1025.3 |
Change in Amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)
Time frame:Baseline to Week 4
change from baseline, improvement
Posted result
| Group | Value (mean), pg/ml | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=10 Participants | -29.9 | 169.6 |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | -40.6 | 97.0 |
| Intranasal Insulin and Empagliflozinn=8 Participants | -26.6 | 43.0 |
| Placebon=9 Participants | -5.1 | 102.4 |
Tau biomarkers
2 endpointsChange in Cerebrospinal Fluid (CSF) Levels of Total Tau
Time frame:Baseline to Week 4
change from baseline, improvement
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau
Time frame:Baseline to Week 4
change from baseline, improvement
Posted result
| Group | Value (mean), pg/ml | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=10 Participants | 2.6 | 52.3 |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | -20.1 | 36.4 |
| Intranasal Insulin and Empagliflozinn=8 Participants | -2.6 | 24.4 |
| Placebon=9 Participants | 7.7 | 33.6 |
Neuroimaging
2 endpointsChange in Total Cerebral Blood Flow (CBF) Using MRI Pseudocontinuous Arterial Spin Labeling (ASL)
Time frame:Baseline to Week 4
change from baseline, improvement
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
| Group | Value (mean), mL/100g/min | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=9 Participants | -0.4 | 5.4 |
| Empagliflozin and Intranasal Insulin Placebon=11 Participants | -1.8 | 5.4 |
| Intranasal Insulin and Empagliflozinn=10 Participants | -0.5 | 2.8 |
| Placebon=8 Participants | 3.9 | 4.5 |
Fluid / digital biomarkers
2 endpointsChange in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181
Time frame:Baseline to Week 4
change from baseline, improvement
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181
Time frame:Baseline to Week 4
change from baseline, improvement
Posted result
| Group | Value (mean), pg/ml | Standard deviation |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=10 Participants | 1.0 | 7.1 |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | -1.9 | 3.8 |
| Intranasal Insulin and Empagliflozinn=8 Participants | 0.3 | 5.5 |
| Placebon=9 Participants | 0.5 | 3.4 |
Safety / tolerability / PK
2 endpointsNumber of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0
Time frame:Week 8
event count, event
Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0
Time frame:Week 8
event count, event
Posted result
| Group | Value (number), participants | Reported bounds |
|---|---|---|
| Intranasal Insulin and Empagliflozin Placebon=13 Participants | 0 | - |
| Empagliflozin and Intranasal Insulin Placebon=12 Participants | 0 | - |
| Intranasal Insulin and Empagliflozinn=11 Participants | 0 | - |
| Placebon=10 Participants | 0 | - |
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
- PMID21514249via BACKGROUND
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- PMID16717171via BACKGROUND
- PMID41057918via DERIVED
Provenance
Sources
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.