Intranasal Insulin and Post-stroke Cognition: A Pilot Study
Condition: Stroke
MeSH terms: Stroke
Intervention: Intranasal Insulin; Intranasal saline
Intervention description: Delivery is with the Vianase device, 20 IU twice daily for 3 weeks.; Delivery is with the Vianase device, 0.5 cc of normal saline
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 40 Years
Maximum age: 89 Years
Healthy volunteers: No

Summary:

      Almost two-thirds of survivors have cognitive impairment (CI), manifested as memory,
      language, and judgement problems. Post-stroke CI at 2 weeks is a significant predictor of
      long-term functional outcome, and more generally, cognitive impairments have a major impact
      on functional outcome and ability to participate in rehabilitation. CI is associated with
      increased systemic inflammation. Intranasally-administered insulin is a promising new therapy
      for enhancing memory in patients with mild cognitive impairment (MCI) and Alzheimer's disease
      (AD), shown in multiple randomized controlled studies. Likely mechanisms of benefit are
      intranasal insulin's ability to restore normal cerebral insulin signaling. Based on the
      overlap in cerebral insulin resistance that occurs in both AD and post-stroke CI, we have
      designed an innovative proof-of-concept, feasibility trial designed to provide pilot data as
      to whether post-stroke survivor CI and caregiver burden is improved with intranasal insulin
      early after stroke. We will explore the impact of intranasal insulin on inflammatory
      biomarkers, since inflammation is a major underlying cause of CI, as shown by others and in
      our preliminary studies of VCAM-1. Specific Aims are: 1. Determine if patients with ischemic
      stroke randomized to intranasal insulin 20 IU BID for 3 weeks have improved cognition,
      compared to patients who receive intranasal saline. Primary outcome is a composite of (a)
      memory and executive function z scores. 2. To assess the impact of intranasal insulin vs
      saline on change in inflammatory biomarker levels (VCAM-1, TNF-alpha, TNFR-I and II) before
      and after the treatment period. 3. To measure differences in burden among caregivers of
      participants in the intranasal insulin vs intranasal saline groups. We will prospectively
      randomize 40 subjects to intranasal insulin (40 IU) vs saline treatment. Following baseline
      cognitive testing 2 weeks post stroke, subjects will receive the assigned treatment for 3
      weeks, followed by a 3-week washout period, with cognitive testing performed after the
      treatment and washout periods and again at 20 weeks. The proposed study will provide data on
      a promising method for treating cognitive function in stroke patients. If effective, our
      pilot data will set the stage for larger phase III clinical trials.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ischemic stroke and measurable deficit on the initial NIHSS (> 1)

          -  Cognitive impairment within the 5th and 50th percentiles for age, race, and education
             based on Montreal Cognitive Assessment (MoCA) or 2 out of 5 delayed recall or less on
             the MoCA.

          -  Able to sign informed consent, have a caregiver, and live within a reasonable driving
             distance from Wake Forest Baptist Medical Center.

        Exclusion Criteria:

          -  Patients under age 40 or 90 years or older

          -  Living in skilled nursing facility

          -  Severe stroke deficits at 4 weeks that prohibit participation in cognitive testing
             (global or receptive aphasia, or severe expressive aphasia)

          -  Diabetes requiring insulin

          -  Psychiatric disorders

          -  Severe head trauma

          -  Alcoholism

          -  Neurologic disorders other than stroke

          -  Renal disease

          -  hepatic disease

          -  chronic obstructive pulmonary disease

          -  unstable cardiac disease

          -  those with prior deficits in ADLs and IADLs