SNIFF - 3-Week Aptar CPS Device

July 25, 2025 updated by: Wake Forest University Health Sciences

Study of Nasal Insulin to Fight Forgetfulness (SNIFF) - 3-Week Aptar CPS Device

The SNIFF 3-Week Aptar Device study will involve using a device to administer insulin or placebo through each participant's nose or intra-nasally. Insulin is a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. This study is measuring how much insulin the device delivers. In addition, this study will look at the effects of insulin or placebo administered intra-nasally using an intranasal delivery device on memory, blood, and cerebrospinal fluid (CSF).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The proposed study will examine whether an intranasal delivery device can be used by adults with preclinical Alzheimer's disease (cognitively normal but with abnormal brain levels of the hallmark peptide Aβ) to reliably deliver insulin or placebo four times daily over a 4 week period. We will also examine effects of treatment on cognition, CSF biomarkers, and cerebral perfusion. If successful, information gained from the study will inform the design of future Phase III trials of intranasal insulin.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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
  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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Humulin® R U-100
Twenty randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive intranasal administrations of Humulin® R U-100 (40 IU) four times daily for 3 weeks.
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.
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.
Placebo Comparator: Placebo
Twenty randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive intranasal administrations of placebo (insulin diluent) four times daily for 3 weeks.
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
Participants will administer placebo (insulin diluent) four times per day with an intranasal delivery device.
Other Names:
  • Insulin Diluent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Prescribed Dose Taken
Time Frame: Week 4
Participant self-reported medication adherence information will be calculated by study staff on a 0%-100% scale. A score below 80% indicates low medication adherence and a score of 80% or higher indicates high medication adherence.
Week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) Z-Score
Time Frame: Baseline to Week 8
Cognition will be measured using the PACC5 scale, which includes the free/cued selective reminding test, delayed paragraph recall, digit-symbol substitution, mini mental state score, and the category fluency task. The PACC5 is a composite score comprised of measures of global cognition, memory, and executive function. The score reflects an averaged z-score, with higher scores indicating better cognitive performance.
Baseline to Week 8
Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog 14) Score
Time Frame: Baseline to Week 8
A psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 65 (worse), and are added to the mean of the words not immediately recalled (max of 10) and the number of items not recalled after a delay (ranging from 0-10) all total the maximum score of 85. A positive change indicates cognitive worsening.
Baseline to Week 8
Change in amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)
Time Frame: Baseline to Week 8
Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 40. CSF Aβ40 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.
Baseline to Week 8
Change in amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)
Time Frame: Baseline to Week 8
Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 42. CSF Aβ42 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.
Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau
Time Frame: Baseline to Week 8
Cerebrospinal fluid (CSF) samples will be used to measure the levels of total tau protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181
Time Frame: Baseline to Week 8
Cerebrospinal fluid (CSF) samples will be used to measure the levels of phospho-tau 181 protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Insulin Levels
Time Frame: Baseline to Week 8
Measurement of the levels of insulin in cerebrospinal fluid (CSF) after being delivered with the intranasal delivery device. This will help to determine the ability of the intranasal delivery device to increase levels of insulin in CSF.
Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 217
Time Frame: Baseline to Week 8
Cerebrospinal fluid (CSF) samples will be used to measure the levels of phospho-tau 217 protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Baseline to Week 8

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quick Dementia Rating Scale (QDRS) Score
Time Frame: Baseline to Week 8
The QDRS (Galvin, 2015) is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (Clinical Dementia Rating score of 0, 0.5, 1, 2, or 3, respectively). The score assesses six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. At Screening the QDRS global score will be used for eligibility purposes. For all other administrations, the 6 domain scores will be summed to get the QDRS Sum of Boxes (SB) score. Sum of boxes score ranges from 0-100 with a high score meaning more severe dementia.
Baseline to Week 8
Change in Patient Health Questionnaire (PHQ-9) Score
Time Frame: Baseline to Week 8
The Patient Health Questionnaire (PHQ-9) is a 9-item, validated measure of depression severity. Respondents indicate how bothered by problems they are on a scale from 0 (not at all) to 3 (nearly every day). Total scores range from 0 to 27, where higher scores indicate more severe depression.
Baseline to Week 8
Change in Generalized Anxiety Disorder scale-7 (GAD-7) Score
Time Frame: Baseline to Week 8
Changes in anxiety will be measured using the Generalized Anxiety Disorder Scale (GAD-7), which contains 7 items with total scores ranging from 0 to 21. Scores of 5, 10, and 15 are cut-offs for mild, moderate, and severe anxiety, respectively.
Baseline to Week 8
Change in PROMIS Sleep Disturbance Questionnaire Score
Time Frame: Baseline to Week 8
A questionnaire to assess self-reported quality of general sleep and sleep disturbance. Each item on the form is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8 to 40 with higher scores indicating greater severity of sleep disturbance.
Baseline to Week 8
Change in the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-ADL-MCI)
Time Frame: Baseline to Week 8
An interview-based assessment of information provided by the study partner (informant). The total scores based on 18 items on the scale range from 0 to 53 with lower scores representing greater impairment.
Baseline to Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Suzanne Craft, PhD, Wake Forest University Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2025

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2031

Study Registration Dates

First Submitted

July 27, 2021

First Submitted That Met QC Criteria

August 13, 2021

First Posted (Actual)

August 16, 2021

Study Record Updates

Last Update Posted (Actual)

July 28, 2025

Last Update Submitted That Met QC Criteria

July 25, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00073876

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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