NCT05081219

SNIFF - Combo INI+EMPA Trial

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: Wake Forest University Health Sciences · Academic / Other
• Sex: All
• Age: 55 Years – 85 Years
• Healthy volunteers: Accepted

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.

Detailed description

The study will consist of a single site, randomized, double-blind trial comparing the effects of 4 weeks of intranasal insulin(40 International Units four times daily), empagliflozin (10 mg daily) and combined intranasal insulin (INI) and empagliflozin (empa) compared with placebo on cerebrospinal fluid (CSF) biomarkers and cognition. At study entry, participants will be randomized to one of 4 conditions: INI, empa, INI+empa or placebo. Participants who are cognitively normal but have abnormal elevations of brain amyloid or who have mild cognitive impairment (MCI) or early Alzheimer's disease (AD) will be enrolled. The primary outcome measure will consist of safety (treatment-related serious adverse events). Secondary outcome measures will consist of cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral blood flow.

Conditions

• Mild Cognitive Impairment
• Cognitive Impairment
• Alzheimer Disease

Interventions

Type	Name	Description
DRUG	Insulin (Humulin® R U-100)	Participants will administer 40 IU of Humulin® U-100 insulin four times per day with an intranasal delivery device.
DRUG	Empagliflozin 10 MG	Participants will be assigned to receive Empagliflozin 10 mg capsules to be taken by mouth once daily.
DEVICE	Aptar Pharma CPS Intranasal Delivery Device	Participants will be assigned to receive Humulin® insulin or placebo administered through the Aptar Pharma CPS intranasal delivery device.
DRUG	Placebo (Insulin Diluent)	Participants will administer placebo (insulin diluent) four times per day with an intranasal delivery device.
DRUG	Placebo (Capsules)	Participants will be assigned to receive placebo capsules (Empagliflozin 10 mg) to be taken by mouth once daily.

Timeline

• Start date: 2021-09-14
• Primary completion: 2024-09-17
• Completion: 2024-09-17
• First posted: 2021-10-18
• Last updated: 2025-10-21
• Results posted: 2025-10-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study