Safety and Effectiveness Study of Intranasal Insulin Glulisine on Cognitive and Memory in Mild-Mod AD Patients.
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Insulin glulisine; Saline
Intervention description: Single treatment, 20 IU/Intranasal (.1ml/10 units Intranasally in each nostril); Single treatment,(saline) 20 IU/Intranasal (.1ml/10units intranasally in each nostril)
Intervention MeSH terms: Insulin glulisine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 65 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Memory; Insulin glulisine; Alzheimer's Disease

Summary:

      The purpose of this study is to investigate the effect of the rapidly acting intranasal
      insulin derivative (glulisine) on memory and cognition in 12 patients suffering from
      mild-moderate Alzheimer's Disease (AD) using a double-blind placebo-controlled single dose
      study. This study will further assess safety of insulin glulisine as well as the effects of
      this drug on olfaction.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subject with a clinical diagnosis of probable AD in accordance with
             National Institute of Neurological and Communicative Disorders and Stroke and the
             Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and
             Dementia Rating Scale (McKhann 1984).

          -  Mini-Mental State Examination (MMSE) score of 18-26.

          -  Hachinski Ischemia Score < 4.

          -  Age is > 65 and <85 years

          -  Females must be > 2 years post-menopausal or surgically sterile.

          -  Must be able to speak, read and understand English in order to comply with testing of
             cognitive function, memory and physiology.

          -  Must have a dedicated family member /caregiver, able to attend all visits and report
             on subject's status.

          -  Subject and family member/caregiver have both provided fully informed written consent
             prior to participation. In the event that subject is legally unable to provide
             informed written consent due to deterioration in cognitive abilities, fully informed
             written consent must be provided by a legally authorized representative.

          -  On a stable dose (≥ 1 months) of a prescribed acetylcholinesterase inhibitor (e.g.
             donepezil, rivastigmine, galantamine) and/or memantine.

          -  A brain CT or MRI in the last 2 years compatible with the diagnosis of probable
             Alzheimer's Disease.

          -  A Clinical Dementia Rating (CDR) ranging from 1 to 2.

        Exclusion Criteria:

          -  Medical history and/or clinically determined evidence of other central nervous system
             (CNS) disorders including brain tumor, active subdural hematoma, seizure disorder,
             multiple sclerosis dementia with Lewy bodies, vascular dementia, corticobasal
             syndrome, progressive supranuclear palsy, Parkinson's disease, multiple system
             atrophy, frontotemporal dementia, normal pressure hydrocephalus, Huntington's disease,
             or Jakob-Creutzfeldt disease presenting as dementia.

          -  Personal medical history and/or clinically determined disorders: current B12
             deficiency, positive syphilis serology, chronic sinusitis or any untreated thyroid
             disease, significant head trauma, or history of difficulty with smell and/or taste
             prior to AD diagnosis.

          -  Diagnosis with any form of diabetes mellitus, actively takes insulin, or has HbA1c >
             6.1 % at screening.

          -  Personal history of any of the following: moderate to severe pulmonary disease,
             congestive heart failure, significant cardiovascular and/or cerebrovascular events in
             previous 6 months, condition known to affect absorption, distribution, metabolism, or
             excretion of drugs such as any hepatic, renal or gastrointestinal disease or any other
             clinically relevant abnormality that inclusion would pose a safety risk to the subject
             as determined by Investigator.

          -  Heavy smoker (defined as smoking half a pack or more per day in the last 10 years
             prior to entry in the study).

          -  Personal history of any psychiatric illness, except major depressive disorder
             (according to Diagnostic and Statistical Manual (DSM)-IV TR) currently in remission or
             stable with treatment for > 2 years, or any other psychiatric condition that inclusion
             would pose a safety risk to the subject as determined by Investigator. Patients with
             active depression (Geriatric Depression Score>9) are excluded from the study.

          -  Currently taking any medications, herbals and food supplements that are determined by
             Investigator to interfere with procedural testing of cognitive function as well as
             ensure study safety.

          -  Recent change (< 1 months) in prescribed acetylcholinesterase inhibitor (e.g.
             donepezil, rivastigmine, galantamine) or memantine.

          -  Current or recent drug or alcohol abuse or dependence defined by DSM-IV TR.

          -  Systolic blood pressure > 160 or < 90 mmHg or diastolic blood pressure > 100 or < 60
             mmHg at Screening.

          -  Screening laboratory results that are medically relevant and which would pose a safety
             risk to the subject as determined by Investigator.

          -  Participation in any other research study at least 3 months prior to this study.

          -  Insulin allergy.

          -  History of significant traumatic brain injury

          -  History of acute and chronic rhinitis and/or sinusitis.

          -  Legally unable to provide informed written consent due to deterioration in cognitive
             abilities.