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Intranasal Insulin and Post-stroke Cognition: A Pilot Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02810392
Recruitment Status : Completed
First Posted : June 23, 2016
Last Update Posted : August 21, 2020
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief 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.

Condition or disease Intervention/treatment Phase
Stroke Drug: Intranasal Insulin Drug: Intranasal saline Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intranasal Insulin and Post-stroke Cognition: A Pilot Study
Actual Study Start Date : April 2016
Actual Primary Completion Date : March 4, 2020
Actual Study Completion Date : March 4, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Intranasal Insulin
Intranasal Insulin (20 IU BID): Humulin insulin packaged is in single-dose ampules and inserted into the VianaseTM chamber. Ampoules are dispensed in 3 week supplies per study visit. Patients/caregivers, investigators, and outcome assessors are masked to group assignment. Subjects will receive their first dose in clinic, and wait 2 hrs to determine any adverse effects of inhaled dose. Glucose levels will be measured to monitor for hypoglycemia and documented. All subjects will check peak dose blood sugar levels with glucometer, 3 times per week during insulin treatment.
Drug: Intranasal Insulin
Delivery is with the Vianase device, 20 IU twice daily for 3 weeks.
Other Name: Humulin insulin

Placebo Comparator: Intranasal Saline
Intranasal saline: Saline is packaged in single-dose ampules and inserted into the VianaseTM chamber. Ampoules are dispensed in 3 week supplies per study visit. Patients/caregivers, investigators, and outcome assessors are masked to group assignment. Subjects will receive their first dose in clinic, and wait 2 hrs to determine any adverse effects of inhaled dose. Glucose levels will be measured to monitor for hypoglycemia and documented. All subjects will check peak dose blood sugar levels with glucometer, 3 times per week during insulin treatment.
Drug: Intranasal saline
Delivery is with the Vianase device, 0.5 cc of normal saline
Other Name: normal saline




Primary Outcome Measures :
  1. Composite of memory z scores [ Time Frame: 3 weeks ]

    Hopkins Verbal Learning Test-Revised (HVLT-R) verbal learning and memory andvailable to facilitate repeat administration in future testing (10 minutes with delay and recognition).

    Brief Visual Memory Test-Revised (BVMT-R)36 is a measure of nonverbal learning and memory captured with immediate and delayed free recall trials, and a recognition memory task (10 minutes with delay and recognition).



Secondary Outcome Measures :
  1. Composite of executive function z scores [ Time Frame: 3 weeks ]
    Trail Making test-A & B, WAIS Digit Span subtest, and WAIS-III Digit-Symbol Coding


Other Outcome Measures:
  1. Story Memory Recall [ Time Frame: 3 weeks ]
    . A narrative of 44 informational bits is read and the recalled information is recorded immediately and after 20 minutes

  2. Instrumental Activities of Daily Living scale: [ Time Frame: 3 weeks ]
    Stroke Impact Scale ADL/IADL scale and the SIS-16

  3. Modified Caregiver Strain Index [ Time Frame: 3 weeks ]
    13 questions related to caregiver strain, administered to caregivers separately from the stroke survivor

  4. Verbal fluency [ Time Frame: 3 weeks ]
    Animal naming and words starting with F, A, and S

  5. Cytokines [ Time Frame: 3 weeks ]
    Tumor necrosis factor (TNF) alpha, TNF Receptor I, TNFR II, Vascular cellular adhesion molecule 1 (VCAM-1)



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810392


Locations
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United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157-1043
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: Cheryl Bushnell, MD Wake Forest University Health Sciences
  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:
Informed Consent Form  [PDF] May 9, 2019

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02810392    
Other Study ID Numbers: IRB00029022
First Posted: June 23, 2016    Key Record Dates
Last Update Posted: August 21, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs