Phase 2
Completed N=47
SNIFF - Combo INI+EMPA Trial
Source: ClinicalTrials.gov NCT05081219 ↗Enrolled (actual)
47
Serious AEs
0.0%
Results posted
Oct 2025
Primary outcomePrimary: Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0 — 0; 0; 0; 0 participants
Summary
The proposed pilot study will provide safety and efficacy preliminary data regarding singular and combined effects of two therapeutic approaches, intranasal insulin and treatment with the sodium-glucose cotransporter type 2 inhibitor (SGLT2i) empagliflozin, to correct bioenergetic and vascular dysfunction in adults with preclinical Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) or early AD.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0 |
0; 0; 0; 0 | — |
| SECONDARY Change in the Preclinical Alzheimer Cognitive Composite V5 (PACC5) Z-Score |
0.2; 0.0; 0.2; -0.1 | — |
| SECONDARY Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score |
-0.5; 1.0; 2.0; 1.2 | — |
| SECONDARY Change in Amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF) |
10.6; -417.2; -159.6; -223.6 | — |
| SECONDARY Change in Amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF) |
-29.9; -40.6; -26.6; -5.1 | — |
| SECONDARY Change in Cerebrospinal Fluid (CSF) Levels of Total Tau |
2.6; -20.1; -2.6; 7.7 | — |
| SECONDARY Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181 |
1.0; -1.9; 0.3; 0.5 | — |
| SECONDARY Change in Total Cerebral Blood Flow (CBF) Using MRI Pseudocontinuous Arterial Spin Labeling (ASL) |
-0.4; -1.8; -0.5; 3.9 | — |
Eligibility Criteria
Inclusion Criteria
- Age 55 to 85 (inclusive)
- Fluent in English
- Cognitively normal or diagnosis of amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD)
- Amyloid positive by positron emission tomography (PET) or cerebrospinal fluid (CSF) criteria
- Stable medical condition for 3 months prior to screening visit
- 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)
- Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician
Exclusion Criteria
- A diagnosis of dementia other than Alzheimer's disease (AD)
- History of a clinically significant stroke
- 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
- Diabetes (type I or type II) insulin-dependent and non-insulin-dependent diabetes mellitus
- Current or past regular use of insulin or any other anti-diabetic medication within 2 months of screening visit
- History of seizure within past five years
- Pregnancy or possible pregnancy
- Use of anticoagulants, unless documentation received from prescribing clinician that anticoagulant medication can be held before lumbar puncture, and approved by study clinician
- Residence in a skilled nursing facility at screening
- Use of an investigational agent within two months of screening visit
- 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)
Data sourced from ClinicalTrials.gov (NCT05081219). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.