The Study of Nasal Insulin in the Fight Against Forgetfulness (SNIFF)
Condition: Amnestic Mild Cognitive Impairment; Alzheimer's Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      An urgent need exists to find effective treatments for Alzheimer's disease (AD) that can
      arrest or reverse the disease at its earliest stages. The emotional and financial burden of
      AD to patients, family members, and society is enormous, and is predicted to grow
      exponentially as the median population age increases. Current FDA-approved therapies are
      modestly effective at best. This study will examine a novel therapeutic approach using
      intranasal insulin (INI) that has shown promise in short-term clinical trials. If successful,
      information gained from the study has the potential to move INI forward rapidly as a therapy
      for AD. The study will also provide evidence for the mechanisms through which INI may produce
      benefits by examining key cerebral spinal fluid (CSF) biomarkers and hippocampal/entorhinal
      atrophy. These results will have considerable clinical and scientific significance, and
      provide therapeutically-relevant knowledge about insulin's effects on AD pathophysiology.
      Growing evidence has shown that insulin carries out multiple functions in the brain, and that
      insulin dysregulation may contribute to AD pathogenesis.

      This study will examine the effects of intranasally-administered insulin on cognition,
      entorhinal cortex and hippocampal atrophy, and cerebrospinal fluid (CSF) biomarkers in
      amnestic mild cognitive impairment (aMCI) or mild AD. It is hypothesized that after 12 months
      of treatment with INI compared to placebo, subjects will improve performance on a global
      measure of cognition, on a memory composite and on daily function. In addition to the
      examination of CSF biomarkers and hippocampal and entorhinal atrophy, the study aims to
      examine whether baseline AD biomarker profile, gender, or Apolipoprotein epsilon 4 (APOE-ε4)
      allele carriage predict treatment response.

      In this study, 240 people with aMCI or AD will be given either INI or placebo for 12 months,
      following an open-label period of 6 months where all participants will be given active drug.
      The study uses insulin as a therapeutic agent and intranasal administration focusing on nose
      to brain transport as a mode of delivery.
    


Intervention name(s): Insulin (Humulin® R U-100); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 20 IU bid taken twice daily (approximately 30 minutes after breakfast and dinner) for a total of 40 IU daily, which will be administered intranasally. The device used to administer insulin releases a metered dose into a chamber covering the participant's nose. The insulin is then inhaled by breathing evenly over a specified period.; Placebo taken twice daily (approximately 30 minutes after breakfast and dinner), which will be administered intranasally. The device used to administer placebo releases a metered dose into a chamber covering the participant's nose. The placebo is then inhaled by breathing evenly over a specified period.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Intranasal insulin; Alzheimer's disease; Amnestic mild cognitive impairment; Dementia; Brain diseases; Memory problems; Mental disorders; Cognitive disorders