Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart (SNIFF-Quick)

This pilot clinical trial will examine the effects of intranasal insulin aspart on cognition, daily function, blood and cerebral spinal fluid markers of Alzheimer's disease, and amyloid deposition in the brain. Participants will be randomly assigned to receive insulin aspart or placebo during a 12-week treatment period.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment; Alzheimer's Disease
• Intervention / Treatment: Drug: Insulin aspart; Drug: Placebo

Detailed Description

A growing body of evidence suggests that insulin plays a role in normal memory processes and that insulin abnormalities may contribute to cognitive and brain changes associated with Alzheimer's disease (AD). Interestingly, insulin administered to the nasal cavity is transported within a few minutes into the brain, but does not affect blood sugar or insulin levels.

This trial will consist of a randomized double-blind, placebo-controlled parallel group trial in which 30 participants with AD or mild cognitive impairment (MCI) receive twice daily intranasal administrations of insulin aspart (20 IU) or placebo (saline), two times per day for 12 weeks. All participants will appoint a "support person" to answer a collateral questionnaire and supervise the administration of the study drug. All participants and study partners will undergo the intensive, structured training program in the self-management of intranasal insulin administration. Cognitive testing and blood collection will occur at baseline, after 6 weeks of treatment, and at the end of the 12 week treatment period. Participants will also receive a lumbar puncture to measure AD biomarkers in the subject's cerebral spinal fluid.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previous or subsequent diagnosis of Alzheimer's disease or mild cognitive impairment
• Ability to communicate in English

Exclusion Criteria:

• Preexisting diabetes
• Clinically significant elevations in liver function test
• Clinically significant elevations in lipid profile
• Prior lumbar lumbar surgeries or other medical conditions that render lumbar punctures unsafe
• Hemoglobin <8 g/dl
• Significant neurologic disease that might affect cognition, other than Alzheimer's disease, including stroke, Parkinson's disease, multiple sclerosis, or recent severe head injury (within the last year) with loss of consciousness >30 minutes or with permanent neurologic sequelae
• Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease
• Current use of antipsychotic, anticonvulsant, anxiolytic, anticoagulant or sedative medications
• Current or previous use of glucose-lowering agents or insulin;
• Chronic use (≥ 3 times per week) of nasal sprays of any type for any indication
• Premenopausal status (defined as having had a period within the last year).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Aspart; Fifteen randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive twice daily intranasal administrations of insulin aspart (20 IU) for 12 weeks.	Drug: Insulin aspart; Participants will administer 20 IU insulin aspart two times per day with an intranasal delivery device.; Other Names: NovoLog Fast-Acting Insulin Aspart
Placebo Comparator: Placebo; Fifteen randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive twice daily intranasal administrations of placebo (saline) for 12 weeks.	Drug: Placebo; Participants will administer placebo two times per day with an intranasal delivery device.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognition	Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog)/mild cognitive impairment (MCI) scores and memory composite (summed Z scores from delayed story and list recall)	6 weeks and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Cerebral spinal fluid (CSF) and blood amyloid-beta, tau protein, and inflammatory markers	Blood - every 6 weeks for 12 weeks; cerebral spinal fluid (CSF) - baseline and week 12
MRI measure of cortical thickness in Alzheimer's disease (AD) -vulnerable regions	Baseline and week 12

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA); General Electric
• Investigators: Principal Investigator: Suzanne Craft, PhD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2015
• Primary Completion (Actual): April 16, 2019
• Study Completion (Actual): April 16, 2019

Study Registration Dates

• First Submitted: June 1, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimated): June 3, 2015

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: IRB00026106; 5P50AG005136-30 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO