Memory Aid by Intranasal Insulin in Diabetes (MemAID)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Regular Human Insulin; Placebo
Intervention description: Regular human insulin 40 IU daily over 24 weeks; Intranasal sterile saline 40 IU daily over 24 weeks
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 289 signed ICF.
244 were randomized (115 T2DM adults and 129 non-DM controls).
79 T2DM adults and 90 non-DM controls completed intervention (as of 4/23/2020)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 289.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Type 2 Diabetes Mellitus; Intranasal Insulin; Placebo; Memory; Gait; Non diabetic older controls

Summary:

      The main purpose of this study is to find the long-term effects of daily administration of 40
      IU of intranasal insulin (INI) as compared to placebo (sterile saline) on cognition and
      memory in people with type 2 diabetes mellitus (DM), and non-diabetic controls over 24 weeks
      with a follow-up period for 24 weeks. Four groups will be tested: DM group treated with INI;
      DM group treated with placebo; control group treated with INI and the control group treated
      with placebo. The INI or placebo will be delivered into the nose. The investigators are
      interested to see whether INI can improve memory and cognition and blood flow in the brain in
      the type 2 DM group as compared to placebo and to the non-diabetic group over a long-term
      period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women aged 50-85 years old

          -  Able to walk for 6 minutes

          -  Diabetes type 2 (DM) group: diagnosis and treatment for type 2 DM with non-insulin
             oral or injectable agents

          -  Non-DM group with similar age range as the DM group, non-diabetic fasting plasma
             glucose (<126 mg/dL) and hemoglobin A1c (HbA1c) (<6.5%)

          -  Participants capable of providing informed consent

        Exclusion Criteria:

          -  Type 2 DM treated with insulin (since 9/25/2017)

          -  Type 1 DM

          -  Intolerance to insulin

          -  History of severe hypoglycemia

          -  Participants who have >1 asymptomatic and/or symptomatic episode of hypoglycemia
             (glucose < 54 mg/dL) during finger stick or plasma glucose (cut off value since
             6/11/2018)

          -  Acute medical condition that required either hospitalization or surgery within the
             past 6 months (e.g., severe hypoglycemia, malignancies, myocardial infarction,stroke)

          -  Liver or renal failure or transplant

          -  Dementia (Mini Mental State Examination [MMSE] scores ≤20)

          -  Current recreational drug or alcohol abuse

          -  Serious systemic disease that would interfere with conduction of clinical trial (mild
             forms of neurological conditions e.g. Parkinson's Disease, autonomic neuropathy etc.
             would be allowed)

          -  Magnetic Resonance Imaging (MRI) substudy in 40 DM patients only: claustrophobia and
             implants incompatible with 3-Tesla MRI

          -  Safety substudy in 20 IDDM patients only: Insulin-treated type 2 diabetics with a
             C-peptide of <0.8 ng/mLd and fasting blood glucose >150 mg/dL will be excluded even
             without history of hypoglycemia during finger stick measurements.