Study of Nasal Insulin to Fight Forgetfulness - Device Study

Study Overview
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Brief Summary
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The SNIFF Device study will involve using a device to administer insulin 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 a nebulizer-like device on memory, blood, and cerebral spinal fluid.

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 placebo delivered with nebulizer-like device on CSF insulin levels, AD biomarkers and memory. At study entry, participants will be randomized to receive either an acute dose of insulin or placebo first, and the other substance 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 test the hypothesis that CSF insulin levels will increase 30 minutes after receiving a 20 International Units dose of insulin delivered with a nebulizer-like device, compared to levels achieved 30 minutes after placebo.

Official Title
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Device Study for Intranasal Delivery of Insulin

Conditions
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Mild Cognitive Impairment, Cognitive Impairment

Intervention / Treatment
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* Drug: Insulin
* Other: Placebo
* Device: intranasal nebulizer-like device


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 use of insulin or any other anti-diabetic medication within 5 years of Screening visit. History of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not exclusionary) 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, antiparkinsonian 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 an acute dose of insulin or of placebo first and the other substance on a second visit.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSF insulin levels | Levels of insulin in CS fluid after being delivered with the device. This will help to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF) | 30 minutes after intervention administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Auditory-Verbal Learning Test (AVLT) | memory measure in which participant hears a list of 12 words over 3 trials, and is asked to recall them immediately after hearing them, then again after a 45 minute delay. Total possible score is 36 for immediate recall and 12 for delayed recall. Higher scores are better. | 5 minutes before lumbar puncture, and immediately following lumbar puncture | 
| CSF Levels of AB42 | Levels of the 42 amino acid isoform of the beta amyloid peptide | 30 minutes after intervention administration | 
| CSF Levels of total tau | Levels of the tau protein | 30 minutes after intervention administration | 
| CSF Levels phospho-tau 181 | Levels of the tau phosphorylated at isotope 181 | 30 minutes after intervention administration | 

 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