Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days (SNIFF-LONG 21)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Suzanne Craft, University of Washington
ClinicalTrials.gov Identifier:
NCT01547169
First received: February 7, 2012
Last updated: December 17, 2012
Last verified: December 2012

February 7, 2012
December 17, 2012
March 2011
December 2012   (final data collection date for primary outcome measure)
Verbal Memory Composite [ Time Frame: Change from Baseline in Verbal Memory at 3 Weeks ] [ Designated as safety issue: No ]
The composite will consist of the weighted sum of Immediate + Delayed Story Recall and Immediate +Delayed List Recall
Same as current
Complete list of historical versions of study NCT01547169 on ClinicalTrials.gov Archive Site
  • Neuropsychological Test of Executive Function 1 [ Time Frame: Change from Baseline in Executive Functioning at 3 Weeks ] [ Designated as safety issue: No ]
    Computerized Dot Counting Test (test of executive functioning)
  • Glucose Tolerance [ Time Frame: Change from Baseline in Glucose Tolerance at 3 Weeks ] [ Designated as safety issue: Yes ]
    Subjects will undergo oral glucose tolerance test (OGTT) to assess glucose tolerance
  • Functional Ability [ Time Frame: Change from Baseline in Functional Ability at 3 Weeks ] [ Designated as safety issue: No ]
    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.
  • Plasma biomarkers of AD [ Time Frame: Change from Baseline in Plasma Biomarkers at 3 Weeks ] [ Designated as safety issue: No ]
    Plasma Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.
  • Neuropsychological Test of Executive Functioning 2 [ Time Frame: Change from Baseline in Executive Functioning at 3 Weeks ] [ Designated as safety issue: No ]
    Computerized Stroop Test
  • Neuropsychological Tests of Visual Working Memory [ Time Frame: Change from Baseline in Visual Working Memory at 3 Weeks ] [ Designated as safety issue: No ]
    Benton Visual Retention Test Form F&G (a test of visual working memory)
Same as current
Not Provided
Not Provided
 
Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days
Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Alzheimer's Disease
  • Mild Cognitive Impairment
  • Drug: Placebo Comparator
    saline, taken twice per day for a 3 week duration
  • Drug: insulin detemir
    10IU of insulin detemir, administered intranasally twice per day for a 3 week duration
    Other Name: Levemir
  • Drug: insulin detemir
    20IU insulin detemir, administered intranasally twice per day for a 3 week duration
    Other Name: Levemir
  • Placebo Comparator: Saline
    Intervention: Drug: Placebo Comparator
  • Experimental: Low Dose Insulin Detemir (10IU bid)
    Intervention: Drug: insulin detemir
  • Experimental: High Dose Insulin Detemir (20IU bid)
    Intervention: Drug: insulin detemir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
December 2012
December 2012   (final data collection date for primary outcome measure)

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
Both
50 Years to 89 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01547169
39683-A, 2P50AG005136-27
Yes
Suzanne Craft, University of Washington
University of Washington
National Institute on Aging (NIA)
Principal Investigator: Suzanne Craft, PhD VA Puget Sound Health Care System; University of Washington School of Medicine
University of Washington
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP