Mechanisms of Insulin Facilitation of Memory

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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).

Official Title
-----------------
Mechanisms of Insulin Facilitation of Memory

Conditions
-----------------
Memory Disorders

Intervention / Treatment
-----------------
* Drug: Insulin
* Other: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of probable AD Age over 21 Clinical Dementia Rating of 0.5 or 1.0 Mini Mental State Exam Score>15 Exclusion Criteria: preexisting diabetes significant neurological disease that might affect cognition, other than AD, including stroke, Parkinson's disease, multiple sclerosis severe head injury with loss of consciousness > 30 minutes or with permanent neurological 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 anti-psychotic or anti-convulsant medications current or previous use of hypoglycemic agents or insulin MRI contraindications claustrophobia pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: insulin<br>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 | Drug: Insulin<br>* 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<br>* Other names: NovoLog, 20 IU;|
| Placebo Comparator: Saline<br>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 | Other: Saline<br>* 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<br>* Other names: Saline, 200 micro liters;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Memory Disorders, Alzheimer's Disease