Clinical trial NCT01547169: Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days
Official title: Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Mild Cognitive Impairment
Keywords: memory
intranasal insulin
Alzheimer's disease
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2012-03-07
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Verbal Memory Composite
timeFrame: Change from Baseline in Verbal Memory at 3 Weeks
Secondary outcomes:
measure: Neuropsychological Test of Executive Function 1
timeFrame: Change from Baseline in Executive Functioning at 3 Weeks
measure: Glucose Tolerance
timeFrame: Change from Baseline in Glucose Tolerance at 3 Weeks
measure: Functional Ability
timeFrame: Change from Baseline in Functional Ability at 3 Weeks
measure: Plasma biomarkers of AD
timeFrame: Change from Baseline in Plasma Biomarkers at 3 Weeks
measure: Neuropsychological Test of Executive Functioning 2
timeFrame: Change from Baseline in Executive Functioning at 3 Weeks
measure: Neuropsychological Tests of Visual Working Memory
timeFrame: Change from Baseline in Visual Working Memory at 3 Weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System; University of Washington School of Medicine
name: Suzanne Craft, PhD
role: PRINCIPAL_INVESTIGATOR
References: