Trial Outcomes & Findings for Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis (NCT NCT02988401)

Last Updated: 2023-03-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

105 participants

Primary outcome timeframe

Up to week 24 visit

Results posted on

2023-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	37	33	35
Overall Study COMPLETED	24	17	28
Overall Study NOT COMPLETED	13	16	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intranasal Insulin 20 International Units n=37 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.	Intranasal Insulin 10 International Units n=33 Participants 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.	Placebo n=35 Participants 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.	Total n=105 Participants Total of all reporting groups
Age, Continuous	53.5 years STANDARD_DEVIATION 10.1 • n=5 Participants	54.4 years STANDARD_DEVIATION 9.2 • n=7 Participants	49.4 years STANDARD_DEVIATION 9.2 • n=5 Participants	52.4 years STANDARD_DEVIATION 9.7 • n=4 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	23 Participants n=7 Participants	22 Participants n=5 Participants	65 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	40 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	31 Participants n=4 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	74 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	37 Participants n=5 Participants	33 Participants n=7 Participants	35 Participants n=5 Participants	105 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to week 24 visit

Population: Individuals with pre-treatment SDMT were included.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=32 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.	Intranasal Insulin 10 International Units n=30 Participants 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.	Placebo n=32 Participants 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.
Change in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT)	0.145 score on a scale Interval 0.0 to 0.29	0.207 score on a scale Interval 0.033 to 0.381	0.163 score on a scale Interval 0.029 to 0.297

SECONDARY outcome

Timeframe: Up to week 24 visit

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=37 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.	Intranasal Insulin 10 International Units n=33 Participants 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.	Placebo n=35 Participants 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.
Number of Participants With Adverse Events Leading to Study Discontinuation	3 Participants	2 Participants	1 Participants

SECONDARY outcome

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

Population: The first 15 participants were included in this safety substudy. One placebo participant was missing the second measurement.

Fingerstick blood glucose levels were monitored twice within the 90 minutes following the first dose administration of study drug for the first 15 participants.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=5 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.	Intranasal Insulin 10 International Units n=5 Participants 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.	Placebo n=5 Participants 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.
Fingerstick Blood Glucose (Subset) First timepoint	97.8 mg/dL Standard Deviation 13.4	95.8 mg/dL Standard Deviation 15.5	90.0 mg/dL Standard Deviation 18.4
Fingerstick Blood Glucose (Subset) Second timepoint	88.4 mg/dL Standard Deviation 8.8	92.2 mg/dL Standard Deviation 15.5	87.8 mg/dL Standard Deviation 11.4

SECONDARY outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline assessment were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=37 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.	Intranasal Insulin 10 International Units n=31 Participants 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.	Placebo n=35 Participants 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.
Change From Baseline in Cognitive Function as Assessed by the Controlled Oral Word Association Test (COWAT)	0.090 score on a scale Interval -0.112 to 0.292	0.070 score on a scale Interval -0.162 to 0.303	0.021 score on a scale Interval -0.174 to 0.216

SECONDARY outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline assessment were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=36 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.	Intranasal Insulin 10 International Units n=31 Participants 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.	Placebo n=35 Participants 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.
Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test, Second Edition (CVLT-II)	0.082 score on a scale Interval 0.015 to 0.149	0.021 score on a scale Interval -0.057 to 0.1	0.020 score on a scale Interval -0.043 to 0.082

SECONDARY outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline assessment were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=36 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.	Intranasal Insulin 10 International Units n=29 Participants 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.	Placebo n=34 Participants 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.
Change From Baseline in Cognitive Function as Assessed by the Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall	0.027 score on a scale Interval -0.02 to 0.074	0.059 score on a scale Interval 0.006 to 0.113	0.030 score on a scale Interval -0.015 to 0.075

SECONDARY outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline assessment were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=36 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.	Intranasal Insulin 10 International Units n=29 Participants 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.	Placebo n=30 Participants 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.
Change in Cognitive Function as Assessed by the Rao-version of the Paced Auditory Serial Addition Test (PASAT)	0.372 score on a scale Interval 0.18 to 0.563	0.363 score on a scale Interval 0.136 to 0.591	0.212 score on a scale Interval 0.027 to 0.398

SECONDARY outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline assessment were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=36 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.	Intranasal Insulin 10 International Units n=29 Participants 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.	Placebo n=35 Participants 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.
Change From Baseline in Cognitive Function as Assessed by the Judgement of Line Orientation Test (JLO)	-0.031 score on a scale Interval -0.109 to 0.046	0.047 score on a scale Interval -0.044 to 0.139	-0.005 score on a scale Interval -0.079 to 0.069

SECONDARY outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline assessment were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=35 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.	Intranasal Insulin 10 International Units n=29 Participants 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.	Placebo n=32 Participants 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.
Change From Baseline in Cognitive Function as Assessed by the Delis-Kaplan Executive Function System Sorting Test	-0.001 score on a scale Interval -0.112 to 0.111	0.027 score on a scale Interval -0.104 to 0.159	0.002 score on a scale Interval -0.114 to 0.118

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline questionnaire were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=31 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.	Intranasal Insulin 10 International Units n=25 Participants 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.	Placebo n=27 Participants 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.
Assess Depression Severity, as Measured by the Beck Depression Inventory-II (BDI-II)	-0.022 score on a scale Interval -0.152 to 0.108	-0.019 score on a scale Interval -0.179 to 0.14	-0.045 score on a scale Interval -0.183 to 0.094

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to week 24 visit

Population: Participants who completed a baseline questionnaire were included.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=36 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.	Intranasal Insulin 10 International Units n=30 Participants 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.	Placebo n=34 Participants 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.
Evaluation of Impact of Study Products on Health Related Quality of Life Using the Functional Assessment of Multiple Sclerosis Questionnaire (FAMS)	0.056 score on a scale Interval -0.277 to 0.389	0.051 score on a scale Interval -0.357 to 0.459	0.240 score on a scale Interval -0.087 to 0.567

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to week 24 visit

Population: Participants who completed the baseline assessment were eligible for inclusion.

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.

Outcome measures

Outcome measures
Measure	Intranasal Insulin 20 International Units n=34 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.	Intranasal Insulin 10 International Units n=30 Participants 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.	Placebo n=33 Participants 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.
Evaluation of How Overall Sleep Quality Impacts People With MS Using a Sleep Questionnaire (Pittsburgh Sleep Quality Index)	-0.026 score on a scale Interval -0.091 to 0.039	0.035 score on a scale Interval -0.035 to 0.105	-0.045 score on a scale Interval -0.11 to 0.021

Adverse Events

Intranasal Insulin 20 International Units

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Intranasal Insulin 10 International Units

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Intranasal Insulin 20 International Units n=37 participants at risk 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 n=33 participants at risk 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.	Placebo n=35 participants at risk 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.
Infections and infestations Urinary Tract Infection	0.00% 0/37 • 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.	3.0% 1/33 • Number of events 2 • 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.	2.9% 1/35 • Number of events 1 • 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.
Infections and infestations Perirectal abscess	0.00% 0/37 • 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.	0.00% 0/33 • 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.	2.9% 1/35 • Number of events 1 • 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.
Injury, poisoning and procedural complications Fall	0.00% 0/37 • 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.	3.0% 1/33 • Number of events 1 • 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.	2.9% 1/35 • Number of events 1 • 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.
Psychiatric disorders Non-epileptic seizure	0.00% 0/37 • 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.	3.0% 1/33 • Number of events 1 • 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.	0.00% 0/35 • 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.
Nervous system disorders Worsening of neurological symptoms	5.4% 2/37 • Number of events 2 • 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.	0.00% 0/33 • 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.	0.00% 0/35 • 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.
Infections and infestations Zoster ophthalmicus	0.00% 0/37 • 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.	0.00% 0/33 • 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.	2.9% 1/35 • Number of events 1 • 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.
Gastrointestinal disorders Small bowel obstruction	2.7% 1/37 • Number of events 1 • 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.	0.00% 0/33 • 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.	0.00% 0/35 • 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.
Cardiac disorders Chest pain	2.7% 1/37 • Number of events 5 • 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.	0.00% 0/33 • 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.	0.00% 0/35 • 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.
Nervous system disorders Multiple sclerosis relapse	0.00% 0/37 • 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.	0.00% 0/33 • 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.	2.9% 1/35 • Number of events 1 • 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.
Nervous system disorders Dizziness	2.7% 1/37 • Number of events 1 • 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.	0.00% 0/33 • 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.	0.00% 0/35 • 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.

Other adverse events

Additional Information

Dr. Ellen Mowry

Johns Hopkins University

Phone: 4106141522

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place