Intranasal Insulin and Post-stroke Cognition: A Pilot Study

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.

Conditions

• Stroke

Interventions

DRUG

Intranasal Insulin

Delivery is with the Vianase device, 20 IU twice daily for 3 weeks.

DRUG

Intranasal saline

Delivery is with the Vianase device, 0.5 cc of normal saline

Sponsors & Collaborators

• Wake Forest University Health Sciences

  lead OTHER

Principal Investigators

• Cheryl Bushnell, MD · Wake Forest University Health Sciences

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

89 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-04-30

Primary Completion

2020-03-04

Completion

2020-03-04

FDA Drug

Yes

Countries

• United States

Study Locations