Intranasal Insulin and Post-stroke Cognition: A Pilot Study
Status:
Completed
Trial end date:
2020-03-04
Target enrollment:
Participant gender:
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.