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

NCT ID: NCT01547169

Last Updated: 2012-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2012-12-31

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.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment

Keywords

memory; intranasal insulin; Alzheimer's disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Saline

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: DRUG

saline, taken twice per day for a 3 week duration

Low Dose Insulin Detemir (10IU bid)

Group Type: EXPERIMENTAL

insulin detemir

Intervention Type: DRUG

10IU of insulin detemir, administered intranasally twice per day for a 3 week duration

High Dose Insulin Detemir (20IU bid)

Group Type: EXPERIMENTAL

insulin detemir

Intervention Type: DRUG

20IU insulin detemir, administered intranasally twice per day for a 3 week duration

Interventions

Placebo Comparator

saline, taken twice per day for a 3 week duration

Intervention Type: DRUG

insulin detemir

10IU of insulin detemir, administered intranasally twice per day for a 3 week duration

Intervention Type: DRUG

insulin detemir

20IU insulin detemir, administered intranasally twice per day for a 3 week duration

Intervention Type: DRUG

Other Intervention Names

Levemir; Levemir

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Craft

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Suzanne Craft, PhD

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System; University of Washington School of Medicine

Locations

VA Puget Sound Health Care System

Seattle, Washington, United States

Countries

United States

Other Identifiers

2P50AG005136-27

Identifier Type: NIH

Identifier Source: secondary_id

View Link

39683-A

Identifier Type: -

Identifier Source: org_study_id