Intervention: Humulin N
Trial phase: Phase 2 | Phase 3
ATC code: A10AE01
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Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 121
Group description: 50% of participants received 20 IU BID intranasal insulin (Humulin® R U-100) twice daily for a total of 40 IU daily for 12 months, followed by a 6-month open label period.
Eligibility criteria:
Inclusion Criteria:

Fluent in English or Spanish
Diagnosis of aMCI by Petersen criteria or probable AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
Mini Mental State Examination (MMSE) score at screening is greater than or equal to 20
Clinical Dementia Rating is 0.5-1 at screening
Logical Memory is less than or equal to 8 for 16 or more years of education, less than or equal to 4 for 8-15 years of education, less than or equal to 2 for 0-7 years of education. Scores measured at screening on Delayed Paragraph Recall (Paragraph A only) from the Wechsler Memory Scale-Revised
Able to complete baseline assessments
Modified Hachinski score of less than or equal to 4
A study partner able to accompany the participant to most visits and answer questions about the participant
The study partner must have direct contact with the participant more than 2 days per week (minimum of 10 hours per week) and provide supervision of drug administration as needed
Stable medical condition for 3 months prior to screening visit
Stable medications for 4 weeks prior to the screening and baseline visits
Stable use of permitted medications
At least six years of education or work history
Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
Visual and auditory acuity adequate for neuropsychological testing

Exclusion Criteria:

A diagnosis of dementia other than probable AD
Probable AD with Down syndrome
History of clinically significant stroke
Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
Sensory impairment that would preclude the participant from participating in or cooperating with the protocol
Diabetes (type 1 or type II) requiring pharmacologic treatment (including both insulin dependent and non-insulin dependent diabetes mellitus)
Current or past use of insulin or any other anti-diabetic medication
Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.
Active neoplastic disease, history of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not excluded)
History of seizure within the past five years
Pregnancy or possible pregnancy
Contraindications to Lumbar Puncture (LP) procedure: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets is less than 100,000 or history of bleeding disorder
Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa) due to LP requirement
Contraindications for MRI (claustrophobia, craniofacial metal implants of any kind, pacemakers)
Residence in a skilled nursing facility at screening
Use of an investigational agent within two months or screening visit
Regular use of narcotics, anticonvulsants, medications with significant anticholinergic activity, antiparkinsonian medications or any other exclusionary medications