Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart

Study Overview
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Brief Summary
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This pilot clinical trial will examine the effects of intranasal insulin aspart on cognition, daily function, blood and cerebral spinal fluid markers of Alzheimer's disease, and amyloid deposition in the brain. Participants will be randomly assigned to receive insulin aspart or placebo during a 12-week treatment period.

Detailed Description
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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. This trial will consist of a randomized double-blind, placebo-controlled parallel group trial in which 30 participants with AD or mild cognitive impairment (MCI) receive twice daily intranasal administrations of insulin aspart (20 IU) or placebo (saline), two times per day for 12 weeks. All participants will appoint a support person to answer a collateral questionnaire and supervise the administration of the study drug. All participants and study partners will undergo the intensive, structured training program in the self-management of intranasal insulin administration. Cognitive testing and blood collection will occur at baseline, after 6 weeks of treatment, and at the end of the 12 week treatment period. Participants will also receive a lumbar puncture to measure AD biomarkers in the subject's cerebral spinal fluid.

Official Title
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Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart

Conditions
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Alzheimer's Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Insulin aspart
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous or subsequent diagnosis of Alzheimer's disease or mild cognitive impairment Ability to communicate in English Exclusion Criteria: Preexisting diabetes Clinically significant elevations in liver function test Clinically significant elevations in lipid profile Prior lumbar lumbar surgeries or other medical conditions that render lumbar punctures unsafe Hemoglobin <8 g/dl Significant neurologic disease that might affect cognition, other than Alzheimer's disease, including stroke, Parkinson's disease, multiple sclerosis, or recent severe head injury (within the last year) with loss of consciousness >30 minutes or with permanent neurologic sequelae Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease Current use of antipsychotic, anticonvulsant, anxiolytic, anticoagulant or sedative medications Current or previous use of glucose-lowering agents or insulin; Chronic use (≥ 3 times per week) of nasal sprays of any type for any indication Premenopausal status (defined as having had a period within the last year).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Aspart<br>Fifteen randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive twice daily intranasal administrations of insulin aspart (20 IU) for 12 weeks. | Drug: Insulin aspart<br>* Participants will administer 20 IU insulin aspart two times per day with an intranasal delivery device.<br>* Other names: NovoLog Fast-Acting Insulin Aspart;|
| Placebo Comparator: Placebo<br>Fifteen randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive twice daily intranasal administrations of placebo (saline) for 12 weeks. | Drug: Placebo<br>* Participants will administer placebo two times per day with an intranasal delivery device.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognition | Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog)/mild cognitive impairment (MCI) scores and memory composite (summed Z scores from delayed story and list recall) | 6 weeks and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral spinal fluid (CSF) and blood amyloid-beta, tau protein, and inflammatory markers |  | Blood - every 6 weeks for 12 weeks; cerebral spinal fluid (CSF) - baseline and week 12 | 
| MRI measure of cortical thickness in Alzheimer's disease (AD) -vulnerable regions |  | Baseline and week 12 |