SNIFF 120: Study of Nasal Insulin to Fight Forgetfulness (120 Days)

Study Overview
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Brief Summary
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The purpose of this study is to find out if insulin, when administered as a nasal spray into the nasal passages, improves memory in adults with mild cognitive impairment (MCI) or Alzheimer's disease.

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 study will consist of a randomized double-blind, placebo-controlled parallel group trial in which 90 participants with AD or MCI receive daily intranasal administrations of either insulin (10 or 20 IU twice a day for a total dose of 20 or 40 IU per day) or placebo (saline twice a day) for 4 months. The study will examine the effects of intranasal insulin administration on cognition, cerebral glucose metabolism, and β-amyloid (Aβ) in cerebrospinal fluid (CSF) and plasma, testing the hypothesis that daily intranasal insulin administration for 4 months will facilitate memory for adults with AD, and adults with mild cognitive impairment (MCI). A subset of participants will have the option to participate in 2 sub-studies: PET scans (prior to and at the end of treatment) to determine whether intranasal insulin increases cerebral glucose metabolism; lumbar punctures (LPs) before and at the end of treatment to determine effects of intranasal insulin administration on CSF Aβ levels.

Official Title
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Therapeutic Effects of Intranasal Insulin Administration in AD

Conditions
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Mild Cognitive Impairment, Alzheimer's Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 55 or greater Good physical health Memory impairment with a diagnosis of mild cognitive impairment (MCI) or Alzheimer's disease (AD) Participants on stable doses of Memantine (Namenda) or cholinesterase inhibitors will be eligible Exclusion Criteria: Chronic sinus problems/allergies with chronic use of nasal decongestants or antihistamines Significant neurologic disease that might affect cognition (other than AD), such as stroke, Parkinson's disease, multiple sclerosis, severe head injury with loss of consciousness for more than 30 minutes or with permanent neurologic symptoms Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease Preexisting diabetes or current or previous use of hypoglycemic agents or insulin; participants will be excluded if they have a fasting blood sugar greater than 165 on baseline OGTT Clinically significant elevations in liver function tests, cholesterol, or triglycerides Major psychiatric disorders (e.g., untreated major depression and schizophrenia) Chronic use of the following types of medications: anti-psychotic, anxiolytic, and opiates

Ages Eligible for Study
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Minimum Age: 55 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 |
| --- | --- |
| Placebo Comparator: 1<br>saline | Drug: Placebo<br>* administered intra-nasally twice a day for 16 weeks<br>* Other names: saline;|
| Experimental: 2<br>10 Units | Drug: Regular Insulin<br>* administered intra-nasally twice a day for 16 weeks<br>* Other names: Novolin U-100;|
| Experimental: 3<br>20 Units | Drug: Regular Insulin<br>* administered intra-nasally twice a day for 16 weeks<br>* Other names: Novolin U-100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cognition |  | every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) | 
| glucose metabolism |  | every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) | 
| plasma biological markers |  | every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSF biological markers |  | every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) | 
| cerebral glucose metabolism |  | every 8 weeks for 16 weeks, again at 8 weeks post-treatment (24 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amyloid protein, brain metabolism, glucose metabolism, insulin sensitivity /resistance, cognition disorders