Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose

Study Overview
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Brief Summary
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The purpose of this study is to find out whether insulin, a drug approved by the FDA for the treatment of diabetes mellitus, reaches the brain and spinal cord when delivered as a nasal spray (intranasally). Intranasal insulin has been shown to improve memory and mood in patients with mild cognitive impairment and dementia, but more evidence is needed to support the ability to effectively target the brain through intranasal routes. 12 healthy adults will be randomly assigned to receive a single dose of either 40 units (low dose group) or 80 units (high dose group) of insulin. Participants will undergo image-guided lumbar puncture (spinal tap) performed by a study radiologist. Samples of cerebrospinal fluid (a fluid surrounding the brain and spinal cord) and blood will be collected at 5 timepoints during the lumbar puncture: once prior to the administration of intranasal insulin, and again at 10, 20, 30, and 40 minutes after the dose is given. Samples will be tested to determine the level of insulin detected in the cerebrospinal fluid and blood at each time point. Results of this study will provide essential information about the ability of the SipNose device to effectively deliver insulin to the central nervous system of humans as measured in the cerebrospinal fluid.

Official Title
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Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose

Conditions
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Healthy

Intervention / Treatment
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* Drug: Low dose Regular Insulin
* Drug: High dose Regular insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is between ≥18 and ≤ 35 years of age Subject's body mass index is between >=18.5 and <=24.9 Subject must be proficient in speaking English to comply with instructions and measures for the study Subject can provide written informed consent Female subjects must have either: (1) a negative pregnancy test at the screening and treatment visits OR (2) be at least 2 years post-menopausal/surgically sterile. Exclusion Criteria: Subject has medical history and/or clinically determined disorders: chronic sinusitis, previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies. Subject has history of any of the following: active and significant central nervous system, psychiatric illness, pulmonary, or cardiovascular disorders or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator Subject has participated in a clinical trial investigation within 3 months of this study. Subject has an insulin allergy Subject has Insulin-dependent diabetes Subject is pregnant or breast feeding Contraindication to spinal tap or other safety factors that preclude lumbar puncture in the investigator's opinion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose Intranasal Insulin<br>One dose of 40 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device. | Drug: Low dose Regular Insulin<br>* Regular insulin administered intranasally at either 40 IU<br>* Other names: Novolin-R;|
| Experimental: High dose Intranasal Insulin<br>One dose of 80 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device. | Drug: High dose Regular insulin<br>* Regular insulin administered intranasally at either 80 IU<br>* Other names: Novolin-R;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Concentration Over Time - Cerebrospinal Fluid | Insulin concentration detected in cerebrospinal fluid at 5 time points (pre-insulin dose; and 10, 20, 30 ,40 minutes after dose). Values will be reported as μIU/mL. Higher values indicate a greater concentration of insulin in the cerebrospinal fluid. Concentrations for each time point (overall and by dose) will be reported as a mean +/- standard error. | 0-40 minutes post-intranasal administration | 
| Cmax of insulin concentration - Cerebrospinal Fluid | CSF insulin concentration will also be reported by Cmax (peak concentration) | 0-40 minutes post-intranasal administration | 
| Tmax of insulin concentration - Cerebrospinal Fluid | CSF insulin concentration will also be reported by Tmax (time of peak concentration) | 0-40 minutes post-intranasal administration | 
| AUC (area under the curve) of insulin concentration - Cerebrospinal Fluid | CSF insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration). | 0-40 minutes post-intranasal administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Concentration Over Time - Serum | Insulin concentration detected in blood at 5 time points (pre-insulin dose; and 10, 20, 30 ,40 minutes after dose). Values will be reported as μIU/mL. Higher values indicate a greater concentration of insulin in the blood. Concentrations for each time point (overall and by dose) will be reported as a mean +/- standard error. Serum insulin concentration will also be reported by Cmax (peak concentration), Tmax (time of peak concentration), and AUC (area under the curve, measured as time x concentration). | 0-40 minutes post-intranasal administration | 
| Cmax of insulin concentration - Serum | Serum insulin concentration will also be reported by Cmax (peak concentration). | 0-40 minutes post-intranasal administration | 
| Tmax of insulin concentration - Serum | Serum insulin concentration will also be reported by Tmax (time of peak concentration). | 0-40 minutes post-intranasal administration | 
| AUC (area under the curve) of insulin concentration - Serum | Serum insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration). | 0-40 minutes post-intranasal administration |