Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days

Mild Cognitive Impairment Clinical Trial

— SNIFF-LONG 21  

Official title:

Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01547169
• Other study ID #: 39683-A
• Secondary ID: 2P50AG005136-27
• Status: Completed
• Phase: Phase 2
• First received: February 7, 2012
• Last updated: December 17, 2012
• Start date: March 2011
• Est. completion date: December 2012

Study information

• Verified date: December 2012
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The study will examine the effects of intranasally administered long-acting insulin detemir on cognition in persons with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI). The rationale for these studies is derived from growing evidence that insulin contributes to multiple brain functions, and that insulin dysregulation can contribute to AD pathogenesis. Thus, therapies aimed at restoring normal insulin signaling in the CNS may have beneficial effects on brain function. Intranasal administration of insulin increases insulin signaling in brain without raising peripheral levels and causing hypoglycemia. Insulin detemir is an insulin analogue that may have better action in brain than other insulin formulations because of its albumin binding properties. The investigators will test the therapeutic effects of intranasally-administered insulin detemir in a dose-finding study in which participants will receive one of two doses of insulin detemir or placebo for a three week period. The investigators will test the hypothesis that either dose will improve memory and daily functioning in persons with AD/aMCI compared with placebo.

Description:

It is well-known that insulin, a hormone that is naturally secreted by the pancreas, plays an important physiological role by regulating blood sugar levels in the body. The investigators now know that insulin plays many important roles in the brain as well. Insulin seems to be especially active in the part of the brain that corresponds to learning and memory. Studies have shown that when people have insufficient insulin in the brain (which, for example, is the case with Type-II diabetes), they are increasingly at risk to develop memory problems and Alzheimer's disease. In a past study, the investigators administered intravenous insulin to participants and found that it improves their memory. However, that particular method would not be a practical intervention for people with Alzheimer's disease due to the risk of hypoglycemia or exacerbation of insulin resistance. Instead, the investigators use an "intranasal" method of administration, in which the insulin is inserted into a device, and administered intranasally. In this method, the insulin travels directly to the brain, and bypasses the body. Our past studies have also demonstrated that this can be a reliable way to improve memory, and it does not change the body's blood glucose levels.

In our past studies, the investigators have used regular insulin, which lasts about 3-4 hours and creates a similar "spike" in insulin that one would have after eating a meal. However, in normal physiology, the pancreas also releases small and more constant "pulses" of insulin throughout the day and night, establishing a base level of insulin. Accordingly, several longer-lasting types of insulin are now available that last closer to 10-12 hours, mimicking that base level of insulin. The current study uses a long-lasting type of insulin called "insulin detemir," to determine if learning and memory will benefit from a more constant supplement of insulin. the investigators want to determine whether this treatment can benefit people who already have a memory impairment—either they already have a diagnosis of Alzheimer's disease or are diagnosed with mild cognitive impairment, a condition that precedes Alzheimer's disease, and whether a lower or higher dose of insulin detemir is more effective. The investigators will examine cognition, daily function, and different markers of Alzheimer's disease that are in the blood as outcome measures.

The investigators have these specific aims:

1. The investigators will test the hypothesis that compared to placebo, three weeks of treatment with intranasal insulin detemir will improve cognition and function in adults with Alzheimer's Disease (AD) or Mild Cognitive Impairment (MCI).

2. The investigators will determine which of two doses of intranasal insulin detemir produces the greatest improvement in cognition and daily function relative to placebo for adults with AD or MCI.

To examine these hypotheses, the investigators are recruiting approximately 60 participants who have been diagnosed with AD or MCI. They will be randomly selected to take a lower dose of insulin detemir, a higher dose of insulin detemir, or saline (which is an inactive substance and will serve as a placebo). Cognition and the level of daily function will be tested before they begin the study drug, and after 3 weeks of the study drug. The investigators will also measure glucose tolerance and take blood samples to measure markers of AD in the blood.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 89 Years

Eligibility

Inclusion Criteria:

• Age 50-89

• Diagnosed with mild cognitive impairment, or mild/moderate AD

Exclusion Criteria:

• Excessively high or low blood pressure, heart rate

• BMI greater than 34

• Pre-existing diabetes not controlled by exercise

• Previous/current use of insulin

• Significant elevations in lipids, liver enzymes

• Menstrual period within the last 12 months

• Significant neurological or medical disorder (other than AD)

• Significant use of nasal decongestants

• Current use of anti-psychotic, anti-convulsive, anxiolytic, glucocorticoids, or sedative medications

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognition Disorders
• Mild Cognitive Impairment

Intervention

Drug:
• Placebo Comparator
saline, taken twice per day for a 3 week duration
• insulin detemir
10IU of insulin detemir, administered intranasally twice per day for a 3 week duration
• insulin detemir
20IU insulin detemir, administered intranasally twice per day for a 3 week duration

Locations

Country	Name	City	State
United States	VA Puget Sound Health Care System	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Verbal Memory Composite	The composite will consist of the weighted sum of Immediate + Delayed Story Recall and Immediate +Delayed List Recall	Change from Baseline in Verbal Memory at 3 Weeks	No
Secondary	Neuropsychological Test of Executive Function 1	Computerized Dot Counting Test (test of executive functioning)	Change from Baseline in Executive Functioning at 3 Weeks	No
Secondary	Glucose Tolerance	Subjects will undergo oral glucose tolerance test (OGTT) to assess glucose tolerance	Change from Baseline in Glucose Tolerance at 3 Weeks	Yes
Secondary	Functional Ability	Subjects will have a collateral informant (i.e., spouse or friend) rate the subjects' ability to carry out activities of daily living on the Dementia Severity Rating Scale.	Change from Baseline in Functional Ability at 3 Weeks	No
Secondary	Plasma biomarkers of AD	Plasma Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.	Change from Baseline in Plasma Biomarkers at 3 Weeks	No
Secondary	Neuropsychological Test of Executive Functioning 2	Computerized Stroop Test	Change from Baseline in Executive Functioning at 3 Weeks	No
Secondary	Neuropsychological Tests of Visual Working Memory	Benton Visual Retention Test Form F&G (a test of visual working memory)	Change from Baseline in Visual Working Memory at 3 Weeks	No