Dose-Dependent Effect of Intranasal Insulin in Humans Using Functional Magnetic Resonance Imaging (fMRI)

Study Overview
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Brief Summary
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The purpose of this trial is to study the brain response using functional MRI (fMRI) before and after varying doses of insulin given through the nose. The magnetic resonance imaging uses a very strong magnet to produce images of participant's brain. It becomes a functional MRI when the study team looks at the activity within the brain (blood flow / change in metabolism).

Detailed Description
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If cardiac arrest is not treated immediately, it causes sudden death. Intranasal insulin may be a way to prevent the brain injury that occurs after a cardiac arrest or other brain injury. Even when immediate treatment gets the heart beating again, many victims remain comatose and die later from brain injury. Nasal insulin reduces brain injury in animal experiments and has been used to try to improve brain degeneration in patients with Alzheimer's disease in doses up to 160 units.

Official Title
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Phase 1, Dose-Dependent Effect of Intranasal Insulin in Humans Using Functional MRI

Conditions
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Healthy

Intervention / Treatment
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* Drug: Intranasal insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants in good health based on medical history, physical exam, and routine laboratory testing Female participants must have a negative urine pregnancy test or be surgically sterilized or postmenopausal. Criteria for menopause are surgical menopause (hysterectomy, oophorectomy) or age > 45 years with the absence of menses for greater than 12 months. Body mass index (BMI) between 18 kg/m2 and 35 kg/m2 Willing and able to stay at the clinical research facility as required by the protocol Willing and able to comply with the investigational nature of the study and able to communicate well with investigators Ability to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines Ability to lie flat for a minimum of 2-hours Exclusion Criteria: Known allergy to insulin. Preexisting diabetes. Current or previous use of diabetes medication or insulin. Any nasal disease or congestion that may interfere with intranasal drug absorption. Baseline hypoglycemia (blood glucose ≤ 65 milligrams per deciliter (mg/dL)) or hyperglycemia (blood glucose > 200 mg/dL) as evident from the screening labs. Active serious disease, such as liver disease, kidney disease, uncontrolled hypertension, clinically significant hypokalemia, and significant or unstable medical illness Treated with an investigational drug within 30 days. Individuals with inadequate venous access. Claustrophobic, uncontrollable shaking, or unable to lie still for a lengthy period. Any metals or implanted devices within the body. Any foreign metallic objects in the body. Females that are pregnant, trying to become pregnant, or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Each volunteer will have 3 study visits, receiving a different study dose at each visit in randomized order as spelled out in the protocol.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal insulin and placebo<br>A total of 3 possible doses will be tested of insulin 0 units (u) (placebo (diluent), 500u, and 1000u. The order that participants will receive these doses will be in a random order. | Drug: Intranasal insulin<br>* Enrolled Participants for this trial will come for 3 study visits. The doses will be administered in varying order: participants will be randomized to one six possible permutations of the intranasal study doses (0, 500, 1000 U) of intranasal insulin at each visit. Participants will undergo a fMRI scan before and after receiving intranasal doses. Additionally, participants will have blood samples taken.<br>* Other names: HUMULIN R U-500;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Signal response using fMRI after administration of intranasal insulin | Values of regions of interest in the fMRI will be calculated for all measures, including cerebral blood flow (CBF), at different used dosages and compared directly as well as with baseline-corrected CBF maps. The study team will determine if a significant difference at different dosages exists. | Baseline fMRI (approximately 30 minutes), fMRI Approximately 30 minutes (after insulin dose administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Glucose (serum or point of care capillary) |  | Baseline (Immediately before drug administration), up to approximately 90 minutes (after drug dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Participants, Intranasal Insulin, Functional Magnetic Resonance Imaging