Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

NCT02988401 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB00095554
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate if giving insulin that is administered in the nostrils (intranasal) is safe and tolerable for people with multiple sclerosis (MS). It is also being done to evaluate if intranasal insulin improves cognitive function in people with MS and to evaluate how it might be working.

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive

Outcome Measures

Primary Outcomes (1)

• Change in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT)

  This task will be performed at five study visits. The SDMT is one of the most commonly used tests to assess processing speed in the MS population and is included in the Minimal Assessment of Cognitive Function in MS (MACFIMS). Higher scores reflect a better outcome (range 0 to 110). In order to account for all contributed data (even for those who did not complete the study but contributed some post-randomization data in the active study phase), the primary analyses include the SDMTs acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the SDMT.

  Up to week 24 visit

Secondary Outcomes (8)

• Number of Participants With Adverse Events Leading to Study Discontinuation

  Up to week 24 visit

• Fingerstick Blood Glucose (Subset)

  At the baseline visit, monitored twice within the 90 minutes following the first dose administration of study drug

• Change From Baseline in Cognitive Function as Assessed by the Controlled Oral Word Association Test (COWAT)

  Up to week 24 visit

• Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test, Second Edition (CVLT-II)

  Up to week 24 visit

• Change From Baseline in Cognitive Function as Assessed by the Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall

  Up to week 24 visit

Other Outcomes (3)

• Assess Depression Severity, as Measured by the Beck Depression Inventory-II (BDI-II)

  Up to week 24 visit

• Evaluation of Impact of Study Products on Health Related Quality of Life Using the Functional Assessment of Multiple Sclerosis Questionnaire (FAMS)

  Up to week 24 visit

• Evaluation of How Overall Sleep Quality Impacts People With MS Using a Sleep Questionnaire (Pittsburgh Sleep Quality Index)

  Up to week 24 visit

Study Arms (3)

Intranasal insulin 20 international units

EXPERIMENTAL

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.

Drug: Insulin

Intranasal insulin 10 international units

EXPERIMENTAL

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.

Drug: Insulin

Intranasal saline

PLACEBO COMPARATOR

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.

Drug: Placebo (Sterile diluent)

Interventions

Insulin DRUG

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; Intranasal insulin 20 international units

Placebo (Sterile diluent) DRUG

All patients will receive either insulin or placebo using Vianase III N2B device during the first 24 weeks of the study.

Intranasal saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets 2010 criteria for MS
• 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

You may not qualify if:

• Current, active major depression
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• United States Department of Defense: collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Related Publications (24)

• 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.

  PMID: 16981607 BACKGROUND

• 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.

  BACKGROUND

• Rao S. Cognitive Function in Patients with Multiple Sclerosis: Impairment and Treatment. IJMSC 2004;1:9-22.

  BACKGROUND

• 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.

  PMID: 23081755 BACKGROUND

• Strober LB, Christodoulou C, Benedict RH, Westervelt HJ, Melville P, Scherl WF, Weinstock-Guttman B, Rizvi S, Goodman AD, Krupp LB. Unemployment in multiple sclerosis: the contribution of personality and disease. Mult Scler. 2012 May;18(5):647-53. doi: 10.1177/1352458511426735. Epub 2011 Dec 19.

  PMID: 22183935 BACKGROUND

• 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.

  PMID: 20830649 BACKGROUND

• Schultheis MT, Weisser V, Ang J, Elovic E, Nead R, Sestito N, Fleksher C, Millis SR. Examining the relationship between cognition and driving performance in multiple sclerosis. Arch Phys Med Rehabil. 2010 Mar;91(3):465-73. doi: 10.1016/j.apmr.2009.09.026.

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• Patti F. Optimizing the benefit of multiple sclerosis therapy: the importance of treatment adherence. Patient Prefer Adherence. 2010 Feb 4;4:1-9. doi: 10.2147/ppa.s8230.

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• Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology. 1991 May;41(5):692-6. doi: 10.1212/wnl.41.5.692.

  PMID: 1823781 BACKGROUND

• Amato MP, Razzolini L, Goretti B, Stromillo ML, Rossi F, Giorgio A, Hakiki B, Giannini M, Pasto L, Portaccio E, De Stefano N. Cognitive reserve and cortical atrophy in multiple sclerosis: a longitudinal study. Neurology. 2013 May 7;80(19):1728-33. doi: 10.1212/WNL.0b013e3182918c6f. Epub 2013 Apr 10.

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• Amato MP, Ponziani G, Siracusa G, Sorbi S. Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. Arch Neurol. 2001 Oct;58(10):1602-6. doi: 10.1001/archneur.58.10.1602.

  PMID: 11594918 BACKGROUND

• Lacy M, Hauser M, Pliskin N, Assuras S, Valentine MO, Reder A. The effects of long-term interferon-beta-1b treatment on cognitive functioning in multiple sclerosis: a 16-year longitudinal study. Mult Scler. 2013 Nov;19(13):1765-72. doi: 10.1177/1352458513485981. Epub 2013 May 7.

  PMID: 23652214 BACKGROUND

• 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.

  PMID: 8021305 BACKGROUND

• 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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• Thornton AE, Raz N, Tucke KA. Memory in multiple sclerosis: contextual encoding deficits. J Int Neuropsychol Soc. 2002 Mar;8(3):395-409. doi: 10.1017/s1355617702813200.

  PMID: 11939698 BACKGROUND

• 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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• Demaree HA, DeLuca J, Gaudino EA, Diamond BJ. Speed of information processing as a key deficit in multiple sclerosis: implications for rehabilitation. J Neurol Neurosurg Psychiatry. 1999 Nov;67(5):661-3. doi: 10.1136/jnnp.67.5.661.

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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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• Solari A, Uitdehaag B, Giuliani G, Pucci E, Taus C. Aminopyridines for symptomatic treatment in multiple sclerosis. Cochrane Database Syst Rev. 2001;2002(4):CD001330. doi: 10.1002/14651858.CD001330.

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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.

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• 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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MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive

Interventions

Insulin

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This study faced major disruptions due to the COVID-19 pandemic. Per IRB, all in-person research activities were halted from mid-March until mid-July 2020. Remote study activities were conducted, where possible. 13 participants who were in the active treatment phase of the study stopped study drug early per DSMB. After re-opening, per IRB request, in-person study visits were restricted to the minimum needed for the main study goals. Thus, there is greater than anticipated missingness.

Results Point of Contact

• Title: Dr. Ellen Mowry
• Organization: Johns Hopkins University

Emowry1@jhmi.edu

4106141522

Study Officials

• Ellen Mowry, MD, MCR

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Scott Newsome, DO

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 9, 2016
• Study Start: December 1, 2017
• Primary Completion: December 17, 2021
• Study Completion: December 17, 2021
• Last Updated: March 10, 2023
• Results First Posted: March 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)