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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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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.
Cognitive impairment is common in and devastating to people with MS. MS is a common, chronic, central nervous system (CNS) disease characterized by inflammation, demyelination, and neurodegeneration. One of the most devastating symptoms of this disease is impaired cognitive function, which is common and present in over 60% of individuals with MS. MS-related cognitive impairment is associated with lowered quality of life and reduced functional capacity, including loss of employment, impaired social relationships, compromised driving safety, and poor adherence to treatment. Impaired cognitive functioning has been observed early in the disease, sometimes even before diagnosis, and cognitive function has been shown to decline longitudinally, both over the short- and long-term. Several cognitive domains are impacted in people with MS, including attention, memory, executive functioning, and especially processing speed.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin | Drug | All patients will receive either insulin or placebo using the Vianase III N2B device during the first 24 weeks of the study. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events Leading to Study Discontinuation | An adverse event will be defined as any occurrence or worsening of an undesirable or unintended sign, symptom (or abnormal laboratory test), or disease temporally associated with the use of a medicinal product or intervention, whether or not it is considered related to the product/intervention. We report overall adverse events in the relevant section. Here, we report adverse events that led to study discontinuation. |
| Measure | Description | Time Frame |
|---|---|---|
| Assess Depression Severity, as Measured by the Beck Depression Inventory-II (BDI-II) | The BDI-II is a 21-question multiple-choice self-report inventory test for measuring the severity of depression. Scores range from zero to 63; higher scores indicate greater depression. 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 analyses include the BDI-II scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the scores. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ellen Mowry, MD, MCR | Johns Hopkins University | Principal Investigator |
| Scott Newsome, DO | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16981607 | Background | 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. | |
| 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. | ||
| 23081755 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | Placebo | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Individuals with pre-treatment SDMT were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
|
AEs and SAEs were collected from the point of randomization until a participant terminated from the study. Unresolved AEs, as well as SAEs, were followed for an added 30 days after study completion. Up to 48 weeks overall.
Adverse events were captured through mixed methods. Subjects were provided with a diary in which to record adverse events. Serious adverse events that were catalogued as such due to hospital admission were also captured systematically if the admission occurred within our hospital system through automated reports to the PI. Other times, the adverse events were captured non-systematically, such as through ad hoc reports to study team members.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ellen Mowry | Johns Hopkins University | 4106141522 | Emowry1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 20, 2020 | Dec 5, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 9, 2022 | Dec 15, 2022 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 17, 2020 | Dec 5, 2022 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| D020528 | Multiple Sclerosis, Chronic Progressive |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| 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. |
|
| Up to week 24 visit |
| Fingerstick Blood Glucose (Subset) | Fingerstick blood glucose levels were monitored twice within the 90 minutes following the first dose administration of study drug for the first 15 participants. | 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) | This test measures phonemic fluency. The test scores the number of words a participant can provide that begin with a specified letter within one minute, such that scores range from zero (worst) to an infinite number (better). Total score is sum of three 60-second trials. 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 COWAT scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test, Second Edition (CVLT-II) | This is a verbal learning and memory test. Scores range from zero to 16; a higher number is better. 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 CVLT-II scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| Change From Baseline in Cognitive Function as Assessed by the Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall | This is a visual, nonverbal test of learning and memory. Scores range from zero to 12; higher is better. 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 analyses include the BVMT-R delayed recall scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| Change in Cognitive Function as Assessed by the Rao-version of the Paced Auditory Serial Addition Test (PASAT) | The Rao-version of the PASAT evaluates processing speed, working memory, and basic addition skills. Scores range from zero to 60; higher is better. Herein we present 3-second PASAT results ("PASAT-3"). 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 analyses include PASAT-3 scores 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 |
| Change From Baseline in Cognitive Function as Assessed by the Judgement of Line Orientation Test (JLO) | Judgment of Line Orientation Test measures a person's ability to match the angle and orientation of lines in space. Scores range from zero to 30; higher is better. 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 analyses include JLO data acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| Change From Baseline in Cognitive Function as Assessed by the Delis-Kaplan Executive Function System Sorting Test | This test measures executive functioning, concept formation, and cognitive flexibility. Scores range from zero to 16; higher is better. 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 analyses include DKEFS correct sort scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| 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) | FAMS is a self-reported health-related quality-of-life instrument for people with multiple sclerosis. Subjects rate six quality-of-life domains: Mobility, Symptoms, Emotional well-being, General contentment, Thinking/fatigue, and Family/social well-being. Scores range from zero to 176; higher scores indicate better health-related quality of life. 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 analyses include the FAMS scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| Evaluation of How Overall Sleep Quality Impacts People With MS Using a Sleep Questionnaire (Pittsburgh Sleep Quality Index) | The sleep questionnaire asks subjects to report various aspects related to their sleep routine. Scores range from zero to 21; higher score indicates worse sleep quality. 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 analyses include the PSQIs acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Up to week 24 visit |
| 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. |
| 22183935 | 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. |
| 20830649 | 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. |
| 20298841 | 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. |
| 20165593 | Background | 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. |
| 1823781 | Background | 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. |
| 23576622 | 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. |
| 11594918 | Background | 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. |
| 23652214 | 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. |
| 8021305 | 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. |
| 9845164 | 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. |
| 11939698 | Background | 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. |
| 15512942 | 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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| 11687106 | Background | 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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| 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. |
| BG002 | Placebo | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
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.
| OG001 | 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. |
| OG002 | Placebo | 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. |
|
|
| Secondary | Number of Participants With Adverse Events Leading to Study Discontinuation | An adverse event will be defined as any occurrence or worsening of an undesirable or unintended sign, symptom (or abnormal laboratory test), or disease temporally associated with the use of a medicinal product or intervention, whether or not it is considered related to the product/intervention. We report overall adverse events in the relevant section. Here, we report adverse events that led to study discontinuation. | Posted | Count of Participants | Participants | Up to week 24 visit |
|
|
|
| Secondary | Fingerstick Blood Glucose (Subset) | Fingerstick blood glucose levels were monitored twice within the 90 minutes following the first dose administration of study drug for the first 15 participants. | The first 15 participants were included in this safety substudy. One placebo participant was missing the second measurement. | Posted | Mean | Standard Deviation | mg/dL | At the baseline visit, monitored twice within the 90 minutes following the first dose administration of study drug |
|
|
|
| Secondary | Change From Baseline in Cognitive Function as Assessed by the Controlled Oral Word Association Test (COWAT) | This test measures phonemic fluency. The test scores the number of words a participant can provide that begin with a specified letter within one minute, such that scores range from zero (worst) to an infinite number (better). Total score is sum of three 60-second trials. 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 COWAT scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed a baseline assessment were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
|
|
|
| Secondary | Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test, Second Edition (CVLT-II) | This is a verbal learning and memory test. Scores range from zero to 16; a higher number is better. 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 CVLT-II scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed a baseline assessment were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
|
|
|
| Secondary | Change From Baseline in Cognitive Function as Assessed by the Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall | This is a visual, nonverbal test of learning and memory. Scores range from zero to 12; higher is better. 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 analyses include the BVMT-R delayed recall scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed a baseline assessment were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
|
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| Secondary | Change in Cognitive Function as Assessed by the Rao-version of the Paced Auditory Serial Addition Test (PASAT) | The Rao-version of the PASAT evaluates processing speed, working memory, and basic addition skills. Scores range from zero to 60; higher is better. Herein we present 3-second PASAT results ("PASAT-3"). 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 analyses include PASAT-3 scores 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. | Participants who completed a baseline assessment were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
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| Secondary | Change From Baseline in Cognitive Function as Assessed by the Judgement of Line Orientation Test (JLO) | Judgment of Line Orientation Test measures a person's ability to match the angle and orientation of lines in space. Scores range from zero to 30; higher is better. 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 analyses include JLO data acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed a baseline assessment were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
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| Secondary | Change From Baseline in Cognitive Function as Assessed by the Delis-Kaplan Executive Function System Sorting Test | This test measures executive functioning, concept formation, and cognitive flexibility. Scores range from zero to 16; higher is better. 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 analyses include DKEFS correct sort scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed a baseline assessment were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
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| Other Pre-specified | Assess Depression Severity, as Measured by the Beck Depression Inventory-II (BDI-II) | The BDI-II is a 21-question multiple-choice self-report inventory test for measuring the severity of depression. Scores range from zero to 63; higher scores indicate greater depression. 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 analyses include the BDI-II scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the scores. | Participants who completed a baseline questionnaire were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
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| Other Pre-specified | Evaluation of Impact of Study Products on Health Related Quality of Life Using the Functional Assessment of Multiple Sclerosis Questionnaire (FAMS) | FAMS is a self-reported health-related quality-of-life instrument for people with multiple sclerosis. Subjects rate six quality-of-life domains: Mobility, Symptoms, Emotional well-being, General contentment, Thinking/fatigue, and Family/social well-being. Scores range from zero to 176; higher scores indicate better health-related quality of life. 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 analyses include the FAMS scores acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed a baseline questionnaire were included. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
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| Other Pre-specified | Evaluation of How Overall Sleep Quality Impacts People With MS Using a Sleep Questionnaire (Pittsburgh Sleep Quality Index) | The sleep questionnaire asks subjects to report various aspects related to their sleep routine. Scores range from zero to 21; higher score indicates worse sleep quality. 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 analyses include the PSQIs acquired within the active treatment phase (from baseline to week 24 visit). We then calculated and report the average change per week in the score. | Participants who completed the baseline assessment were eligible for inclusion. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to week 24 visit |
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| 0 |
| 37 |
| 5 |
| 37 |
| 24 |
| 37 |
| EG001 | 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. | 0 | 33 | 3 | 33 | 18 | 33 |
| EG002 | Placebo | 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. | 0 | 35 | 5 | 35 | 18 | 35 |
| Perirectal abscess | Infections and infestations | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Non-epileptic seizure | Psychiatric disorders | Non-systematic Assessment |
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| Worsening of neurological symptoms | Nervous system disorders | Non-systematic Assessment |
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| Zoster ophthalmicus | Infections and infestations | Non-systematic Assessment |
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| Small bowel obstruction | Gastrointestinal disorders | Non-systematic Assessment |
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| Chest pain | Cardiac disorders | Non-systematic Assessment |
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| Multiple sclerosis relapse | Nervous system disorders | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Irritability | Psychiatric disorders | Non-systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Upper respiratory infection | Infections and infestations | Non-systematic Assessment |
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| Sore throat | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | Non-systematic Assessment |
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| Nightmare | Psychiatric disorders | Non-systematic Assessment |
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| Pain | General disorders | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Weakness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Memory impairment | Nervous system disorders | Non-systematic Assessment |
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| Fracture | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Paresthesia | Nervous system disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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Not provided
Not provided
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| Second timepoint |
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