Mechanisms of Insulin Facilitation of Memory

• Sponsor: University of Texas at Austin (Other)
• Overall Status: Completed
• CT.gov ID: NCT01145482
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Memory Disorders	Drug: Insulin; Other: Saline	N/A

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Mechanisms of Insulin Facilitation of Memory
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: 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; Other Names: NovoLog, 20 IU
Placebo Comparator: 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	Other: 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; Other Names: Saline, 200 micro liters

Outcome Measures

Primary Outcome Measures

1. Cerebral Glutamate Concentration [15 minutes post insulin or placebo administration]

   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.

Secondary Outcome Measures

1. Memory [15 minutes post insulin or placebo administration]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of texas at Austin	Austin	Texas	United States	78712

Sponsors and Collaborators

• University of Texas at Austin

Investigators

• Principal Investigator: Andreana P Haley, PhD, University of Texas at Austin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Andreana P. Haley, Assistant Professor, University of Texas at Austin
• ClinicalTrials.gov Identifier: NCT01145482
• Other Study ID Numbers: 2010-05-0007
• First Posted: Jun 16, 2010
• Last Update Posted: Nov 2, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Andreana P. Haley, Assistant Professor, University of Texas at Austin: Memory Disorders; Alzheimer's Disease
• Additional relevant MeSH terms: Memory Disorders; Insulin; Insulin Aspart

Study Results

Participant Flow

Arm/Group Title	Insulin First, Then Saline	Saline First, Then Insulin
Arm/Group Description	20 IU of insulin was administered once daily on two occasions followed by 200 micro liters of saline once daily on two occasions	200 micro liters of saline was administered once daily on two occasions followed by 20 IU of insulin once daily on two occasions
Period Title: First Intervention (1 Day)
STARTED	6	6
COMPLETED	6	5
NOT COMPLETED	0	1
Period Title: First Intervention (1 Day)
STARTED	5	6
COMPLETED	5	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Insulin First, Then Saline	Saline First, Then Insulin	Total
Arm/Group Description	20 IU of insulin was administered once daily on two occasions followed by 200 micro liters of saline administered once daily on two occasions	200 micro liters of saline was administered once daily on two occasions followed by 20 IU of insulin administered once daily on two occasions	Total of all reporting groups
Overall Participants	5	6	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.8 (8.58)	74.33 (5.92)	74.09 (6.54)
Sex: Female, Male (Count of Participants)
Female	3 60%	2 33.3%	5 45.5%
Male	2 40%	4 66.7%	6 54.5%

Outcome Measures

1. Primary Outcome

Title	Cerebral Glutamate Concentration
Description	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.
Time Frame	15 minutes post insulin or placebo administration

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Insulin	Saline
Arm/Group Description	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	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
Measure Participants	11	11
Mean (Standard Deviation) [ratio]	1.34 (0.12)	1.34 (0.17)

2. Secondary Outcome

Title	Memory
Description	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
Time Frame	15 minutes post insulin or placebo administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin	Saline
Arm/Group Description	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	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
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	6.73 (6.25)	5.36 (2.69)

Adverse Events

Time Frame	immediately following study visits
Arm/Group Title	Insulin		Saline
Arm/Group Description	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		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
All Cause Mortality
	Insulin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Insulin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		1/11 (9.1%)
Gastrointestinal disorders
nausea and urge to vomit	0/11 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.