Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days
Condition: Alzheimer's Disease; Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Placebo Comparator; insulin detemir; insulin detemir
Intervention type(s): Drug; Drug; Drug
Intervention description(s): saline, taken twice per day for a 3 week duration; 10IU of insulin detemir, administered intranasally twice per day for a 3 week duration; 20IU insulin detemir, administered intranasally twice per day for a 3 week duration
Other intervention name(s): Levemir; Levemir
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Detemir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: memory; intranasal insulin; Alzheimer's disease