SNIFF Multi-Device Study 2

Study Overview
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Brief Summary
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The SNIFF Device study will involve using one of three devices to administer insulin through each participant's nose or intra-nasally, accompanied by a lumbar puncture. This goal of this study is to measure how much insulin the device delivers to the cerebrospinal fluid (CSF). In addition, this study will look at the effects of insulin administered intra-nasally on memory, and on blood levels of insulin.

Detailed Description
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The aim of this study is to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF). 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. The study will consist of a single site, randomized, double-blind trial comparing the acute effects of INI 20 International Units or 40 International Units delivered with one of three nebulizer-like devices on CSF insulin levels, AD biomarkers and memory. At study entry, participants will be randomized to receive either 20 or 40 IU insulin first, and the opposite dose on a second visit. Participants who are cognitively normal or who have aMCI (n=30) will be enrolled. The primary outcome measure will be to establish which device and which dose provides the greatest increase in CSF insulin which will provide important evidence to be used in the design of future trials.

Official Title
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SNIFF Multi-Device Study 2 - Study of Nasal Insulin to Fight Forgetfulness

Conditions
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Mild Cognitive Impairment, Cognitive Impairment

Intervention / Treatment
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* Drug: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
* Drug: 40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fluent in English Cognitively normal or diagnosis of aMCI Stable medical condition for 3 months prior to screening visit Stable medications for 4 weeks prior to the screening and study visits 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 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 warfarin (Coumadin) and dabigatran (Pradaxa) 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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: At study entry, participants will be randomized to receive either 20 or 40 International Units of insulin first and the opposite substance on a second visit.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 IU Insulin first, then 40 IU Insulin<br>Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive regular insulin (U100, 40 IU) at visit 3 during second intervention period. | Drug: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)<br>* Participants will be assigned to receive regular insulin either 20 or 40 IU administered through an intranasal nebulizer-like device.<br>* Other names: Humulin® R U-100;|
| Experimental: 40 IU Insulin first, then 20 IU Insulin<br>Participants will be randomly assigned to receive regular insulin (U100, 40 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive regular insulin (U100, 20 IU) at visit 3 during second intervention period. | Drug: 40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)<br>* Participants will be assigned to receive regular insulin either 40 or 20 IU administered through an intranasal nebulizer-like device.<br>* Other names: Humulin® R U-100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSF insulin levels | To compare changes in CSF insulin levels after receiving a 20 or 40 International Unit dose of insulin delivered with one of three devices, compared to baseline levels. | 30 minutes after intervention administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Auditory-Verbal Learning Test (AVLT) | To examine differences in memory performance measured with a list learning test (Auditory Verbal Learning Test) after administration of 20 or 40 IU insulin. | 5 minutes before lumbar puncture, and immediately following lumbar puncture. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal Delivery of Insulin, Cognitive Testing, Nasal Insulin