Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis
NCT ID: NCT02988401
Last Updated: 2023-03-10
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
105 participants
INTERVENTIONAL
2017-12-01
2021-12-17
Brief Summary
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Detailed Description
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To date, multiple pharmacologic interventions have been assessed with disappointing results. There was no significant difference between treatment and placebo for cognition in randomized control trials of donepezil, aminopyridines, gingko biloba, and memantine. Psychostimulants demonstrated some efficacy, but only in secondary outcome measures. Behavioral interventions show promise but are understudied. Furthermore, cognitive rehabilitation is often time consuming, costly, and not universally available. Hence, there is an urgent need to identify or develop novel therapies that can help improve cognitive function in MS.
Intranasal insulin is extremely safe and tolerable in other populations, allowing for concentrated delivery to the nervous system. An intranasal delivery system provides a non-invasive way to bypass the blood-brain barrier and allow rapid delivery of a medication to the CNS via the olfactory and trigeminal perivascular channels.The main advantage of the delivery system is reducing systemic side effects via limiting a medication's exposure to peripheral organs and tissues.
Insulin administration has been shown to improve memory and learning in healthy people and in those with neurodegenerative diseases. Intranasal insulin has been shown to have neuroprotective and restorative effects in several human clinical trials. Overall, findings suggest that intranasal insulin not only affects cognitive function acutely, but that over time, there may be associated structural changes that lead to a more permanent treatment benefit. Cognitive dysfunction is very common in MS and can be devastating, therefore a treatment intervention (i.e., intranasal insulin) can help both acutely and longitudinally.
The primary aim of this study is to assess the safety and tolerability of intranasal insulin in people with MS. The secondary aim is to evaluate if intranasal insulin improves learning and memory in people with MS. The third aim is to evaluate the impact of intranasal insulin on measures of oxidative stress, axonal injury, cellular stress, and energy metabolism in MS.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Intranasal insulin 20 international units
Subjects will administer 20 I.U. of insulin in the nostrils using a ViaNaseTM controlled particle dispersion nasal device two times/day (BID) for 24 weeks.
Insulin
All patients will receive either insulin or placebo using the Vianase III N2B device during the first 24 weeks of the study.
Intranasal insulin 10 international units
Subjects will administer 10 I.U. of insulin in the nostrils using a ViaNaseTM controlled particle dispersion nasal device two times/day (BID) for 24 weeks.
Insulin
All patients will receive either insulin or placebo using the Vianase III N2B device during the first 24 weeks of the study.
Intranasal saline
Subjects will administer a sterile diluent containing inactive ingredients in the nostrils using a ViaNaseTM controlled particle dispersion nasal device two times/day (BID) for 24 weeks.
Placebo (Sterile diluent)
All patients will receive either insulin or placebo using Vianase III N2B device during the first 24 weeks of the study.
Interventions
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Insulin
All patients will receive either insulin or placebo using the Vianase III N2B device during the first 24 weeks of the study.
Placebo (Sterile diluent)
All patients will receive either insulin or placebo using Vianase III N2B device during the first 24 weeks of the study.
Eligibility Criteria
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Inclusion Criteria
* No relapse in past 3 months
* At least mild cognitive impairment (based off of SDMT/PST score)
* Capacity to learn and self-administer intranasal insulin/placebo, or presence of a caregiver with such capacity who is willing to do it for the duration of the trial
* Untreated/on the same MS therapy for at least 6 months, with no anticipated change in the next year
* Willing to prevent pregnancy during study if female of childbearing potential
Exclusion Criteria
* No tricyclic antidepressant or anticonvulsant (except carbamazepine, pregabalin or gabapentin) use within 6 weeks of screening; if on oxybutynin or tolterodine, on stable dose for \> 6 months without plans for changing dose in next year
* If taking selective serotonin (± norepinephrine) reuptake inhibitors, pregabalin, gabapentin, sympathomimetic, monoamine oxidase inhibitor, antipsychotic, amantadine, cholinesterase inhibitor, memantine, modafanil, armodafinil, or evening short-acting benzodiazepines, on stable dose for 6 weeks or greater
* Pregnant or nursing
* THC; illicit drug or alcohol abuse in past 3 months
* History of diabetes mellitus or insulin resistance
* Active liver disease, stage IV/V kidney disease or severe metabolic derangements
* CNS disorder other than MS or headache
18 Years
70 Years
ALL
No
Sponsors
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United States Department of Defense
FED
Johns Hopkins University
OTHER
Responsible Party
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Principal Investigators
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Ellen Mowry, MD, MCR
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University
Scott Newsome, DO
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University
Locations
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Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Countries
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References
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Benedict RH, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, Weinstock-Guttman B. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc. 2006 Jul;12(4):549-58. doi: 10.1017/s1355617706060723.
DeLuca J. What we know about cognitive changes in multiple sclerosis. In: LaRocca N, Kalb R, eds. Multiple Sclerosis: Understanding the Cognitive Challenges. New York: Demos Health; 2006: 17-40.
Rao S. Cognitive Function in Patients with Multiple Sclerosis: Impairment and Treatment. IJMSC 2004;1:9-22.
Ruet A, Deloire M, Hamel D, Ouallet JC, Petry K, Brochet B. Cognitive impairment, health-related quality of life and vocational status at early stages of multiple sclerosis: a 7-year longitudinal study. J Neurol. 2013 Mar;260(3):776-84. doi: 10.1007/s00415-012-6705-1. Epub 2012 Oct 19.
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Morrow SA, Drake A, Zivadinov R, Munschauer F, Weinstock-Guttman B, Benedict RH. Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline. Clin Neuropsychol. 2010 Oct;24(7):1131-45. doi: 10.1080/13854046.2010.511272. Epub 2010 Sep 8.
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DeLuca J, Barbieri-Berger S, Johnson SK. The nature of memory impairments in multiple sclerosis: acquisition versus retrieval. J Clin Exp Neuropsychol. 1994 Apr;16(2):183-9. doi: 10.1080/01688639408402629.
DeLuca J, Gaudino EA, Diamond BJ, Christodoulou C, Engel RA. Acquisition and storage deficits in multiple sclerosis. J Clin Exp Neuropsychol. 1998 Jun;20(3):376-90. doi: 10.1076/jcen.20.3.376.819.
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DeLuca J, Chelune GJ, Tulsky DS, Lengenfelder J, Chiaravalloti ND. Is speed of processing or working memory the primary information processing deficit in multiple sclerosis? J Clin Exp Neuropsychol. 2004 Jun;26(4):550-62. doi: 10.1080/13803390490496641.
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Krupp LB, Christodoulou C, Melville P, Scherl WF, Pai LY, Muenz LR, He D, Benedict RH, Goodman A, Rizvi S, Schwid SR, Weinstock-Guttman B, Westervelt HJ, Wishart H. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology. 2011 Apr 26;76(17):1500-7. doi: 10.1212/WNL.0b013e318218107a.
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Lovera JF, Kim E, Heriza E, Fitzpatrick M, Hunziker J, Turner AP, Adams J, Stover T, Sangeorzan A, Sloan A, Howieson D, Wild K, Haselkorn J, Bourdette D. Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial. Neurology. 2012 Sep 18;79(12):1278-84. doi: 10.1212/WNL.0b013e31826aac60. Epub 2012 Sep 5.
Lovera JF, Frohman E, Brown TR, Bandari D, Nguyen L, Yadav V, Stuve O, Karman J, Bogardus K, Heimburger G, Cua L, Remingon G, Fowler J, Monahan T, Kilcup S, Courtney Y, McAleenan J, Butler K, Wild K, Whitham R, Bourdette D. Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial. Mult Scler. 2010 Jun;16(6):715-23. doi: 10.1177/1352458510367662. Epub 2010 May 18.
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Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. doi: 10.1001/archneurol.2011.233. Epub 2011 Sep 12.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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IRB00095554
Identifier Type: -
Identifier Source: org_study_id
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