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The study described in the present application will test the hypothesis that insulin mediated facilitation of memory in Alzheimer's disease (AD) is achieved through enhanced glutamatergic neurotransmission due to improvements in cerebral glucose metabolism. The effect of a single dose of intranasal insulin on memory and cerebral glutamate concentrations in adults with mild AD or amnestic mild cognitive impairment (aMCI), the presumed prodromal phase of AD will be studied. Successful completion of this study may set the stage for a larger-scale treatment trial of intranasal insulin for adults with memory disorders. However, the use of insulin in this manner at this point in time is purely experimental.
The specific aims of this project will be accomplished through a cross sectional repeated measures design in which 15 participants with mild AD or amnestic MCI will undergo assessments of brain structure and function 15 minutes after a single dose of insulin (20 IU) or placebo. Insulin and placebo conditions will be counterbalanced across participants.
Intranasal insulin or placebo administration: Saline and insulin (NovoLog) will be ordered though the UT Student Health Services Pharmacy (Sharon Roberson, Chief Pharmacist) and stored at 4°C, according to standard pharmacy protocols. Three ml doses of saline or insulin will be packaged in nasal spray bottles (e.g., Spectrum Pharmacy Products bottles 969-17404P and actuators 551-24362P) designed to deliver 100μL dose with each spray. A total volume of 200μL will be delivered during each administration (one 100μL dose in each nostril).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| insulin | Experimental | 20 IU of insulin was administered once daily on two occasions in either the first intervention period or second intervention period using a nasal spray bottle |
|
| Saline | Placebo Comparator | 200 micro liters of saline was administered once daily on two separate occasions in either the first intervention period or second intervention period using a nasal spray bottle |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin | Drug | 20 IU of insulin was administered once daily on two occasions in either the first intervention period or second intervention period using a nasal spray bottle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cerebral Glutamate Concentration | Glutamate concentration was expressed as the ratio of glutamate to creatine. This was determined using magnetic resonance spectroscopy (MRS), a magnetic resonance technique that uses the same equipment as magnetic resonance imaging (MRI), but allows researchers to extract information about the concentrations of various neurochemicals of neurobiological significance. | 15 minutes post insulin or placebo administration |
| Measure | Description | Time Frame |
|---|---|---|
| Memory | Memory performance was assessed using delayed recall (number of units recalled) on the Wechsler Memory Scale (WMS-IV) logical memory (story recall) test. Scores represent a sum of recalled units of two different stories after a 30 minute delay. Total scores range from 0 to 50 (0-25 for each story) with higher scores reflecting better memory performance | 15 minutes post insulin or placebo administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andreana P Haley, PhD | University of Texas at Austin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of texas at Austin | Austin | Texas | 78712 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Insulin First, Then Saline | 20 IU of insulin was administered once daily on two occasions followed by 200 micro liters of saline once daily on two occasions |
| FG001 | Saline First, Then Insulin | 200 micro liters of saline was administered once daily on two occasions followed by 20 IU of insulin once daily on two occasions |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
|
| ||||||||||||||||||
| Second Intervention (1 Day) |
|
Mean age 74.09, SD = 6.54 Gender, Female = 5, Male = 6
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| ID | Title | Description |
|---|---|---|
| BG000 | Insulin First, Then Saline | 20 IU of insulin was administered once daily on two occasions followed by 200 micro liters of saline administered once daily on two occasions |
| BG001 | Saline First, Then Insulin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cerebral Glutamate Concentration | Glutamate concentration was expressed as the ratio of glutamate to creatine. This was determined using magnetic resonance spectroscopy (MRS), a magnetic resonance technique that uses the same equipment as magnetic resonance imaging (MRI), but allows researchers to extract information about the concentrations of various neurochemicals of neurobiological significance. | per protocol | Posted | Mean | Standard Deviation | ratio | 15 minutes post insulin or placebo administration |
|
immediately following study visits
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Insulin | 20 IU of insulin was administered once daily on two occasions in either the first intervention period or second intervention period using a nasal spray bottle |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea and urge to vomit | Gastrointestinal disorders | MedDRA v12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Andreana Haley | The University of Texas at Austin | 512-232-0863 | haley@psy.utexas.edu |
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| ID | Term |
|---|---|
| D008569 | Memory Disorders |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| D061267 | Insulin Aspart |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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|
| Saline | Other | 200 micro liters of saline was administered once daily on two separate occasions in either the first intervention period or second intervention period using a nasal spray bottle |
|
|
| NOT COMPLETED |
|
200 micro liters of saline was administered once daily on two occasions followed by 20 IU of insulin administered once daily on two occasions
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
200 micro liters of saline was administered once daily on two separate occasions in either the first intervention period or second intervention period using a nasal spray bottle |
|
|
| Secondary | Memory | Memory performance was assessed using delayed recall (number of units recalled) on the Wechsler Memory Scale (WMS-IV) logical memory (story recall) test. Scores represent a sum of recalled units of two different stories after a 30 minute delay. Total scores range from 0 to 50 (0-25 for each story) with higher scores reflecting better memory performance | Posted | Mean | Standard Deviation | units on a scale | 15 minutes post insulin or placebo administration |
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | Saline | 200 micro liters of saline was administered once daily on two separate occasions in either the first intervention period or second intervention period using a nasal spray bottle | 0 | 11 | 1 | 11 |
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061266 | Insulin, Short-Acting |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |