Last reviewed · How we verify

NCT02988401

Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

Completed Phase 1, PHASE2 Results posted Last updated 10 March 2023
What this trial tests

Phase 1, PHASE2 trial testing Insulin in Multiple Sclerosis, Relapsing-Remitting in 105 participants. Completed in 17 December 2021.

Timeline
1 December 2017
Primary endpoint
17 December 2021
17 December 2021

Quick facts

Lead sponsorJohns Hopkins University
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment105
Start date1 December 2017
Primary completion17 December 2021
Estimated completion17 December 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Johns Hopkins University

Who can join

Adults 18 to 70, any sex, with Multiple Sclerosis, Relapsing-Remitting or Multiple Sclerosis, Secondary Progressive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT) Primary · Up to week 24 visit

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 a

GroupValue95% CI
Intranasal Insulin 20 International Units0.1450.000 – 0.290
Intranasal Insulin 10 International Units0.2070.033 – 0.381
Placebo0.1630.029 – 0.297
Number of Participants With Adverse Events Leading to Study Discontinuation Secondary · 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.

GroupValue95% CI
Intranasal Insulin 20 International Units3
Intranasal Insulin 10 International Units2
Placebo1
Fingerstick Blood Glucose (Subset) Secondary · At the baseline visit, monitored twice within the 90 minutes following the first dose administration of study drug

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

First timepoint
GroupValue95% CI
Intranasal Insulin 20 International Units97.8± 13.4
Intranasal Insulin 10 International Units95.8± 15.5
Placebo90.0± 18.4
Second timepoint
GroupValue95% CI
Intranasal Insulin 20 International Units88.4± 8.8
Intranasal Insulin 10 International Units92.2± 15.5
Placebo87.8± 11.4
Change From Baseline in Cognitive Function as Assessed by the Controlled Oral Word Association Test (COWAT) Secondary · Up to week 24 visit

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 averag

GroupValue95% CI
Intranasal Insulin 20 International Units0.090-0.112 – 0.292
Intranasal Insulin 10 International Units0.070-0.162 – 0.303
Placebo0.021-0.174 – 0.216
Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test, Second Edition (CVLT-II) Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units0.0820.015 – 0.149
Intranasal Insulin 10 International Units0.021-0.057 – 0.100
Placebo0.020-0.043 – 0.082
Change From Baseline in Cognitive Function as Assessed by the Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units0.027-0.020 – 0.074
Intranasal Insulin 10 International Units0.0590.006 – 0.113
Placebo0.030-0.015 – 0.075
Change in Cognitive Function as Assessed by the Rao-version of the Paced Auditory Serial Addition Test (PASAT) Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units0.3720.180 – 0.563
Intranasal Insulin 10 International Units0.3630.136 – 0.591
Placebo0.2120.027 – 0.398
Change From Baseline in Cognitive Function as Assessed by the Judgement of Line Orientation Test (JLO) Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units-0.031-0.109 – 0.046
Intranasal Insulin 10 International Units0.047-0.044 – 0.139
Placebo-0.005-0.079 – 0.069
Change From Baseline in Cognitive Function as Assessed by the Delis-Kaplan Executive Function System Sorting Test Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units-0.001-0.112 – 0.111
Intranasal Insulin 10 International Units0.027-0.104 – 0.159
Placebo0.002-0.114 – 0.118
Assess Depression Severity, as Measured by the Beck Depression Inventory-II (BDI-II) Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units-0.022-0.152 – 0.108
Intranasal Insulin 10 International Units-0.019-0.179 – 0.140
Placebo-0.045-0.183 – 0.094
Evaluation of Impact of Study Products on Health Related Quality of Life Using the Functional Assessment of Multiple Sclerosis Questionnaire (FAMS) Secondary · Up to week 24 visit

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

GroupValue95% CI
Intranasal Insulin 20 International Units0.056-0.277 – 0.389
Intranasal Insulin 10 International Units0.051-0.357 – 0.459
Placebo0.240-0.087 – 0.567
Evaluation of How Overall Sleep Quality Impacts People With MS Using a Sleep Questionnaire (Pittsburgh Sleep Quality Index) Secondary · Up to week 24 visit

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.

GroupValue95% CI
Intranasal Insulin 20 International Units-0.026-0.091 – 0.039
Intranasal Insulin 10 International Units0.035-0.035 – 0.105
Placebo-0.045-0.110 – 0.021

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Intranasal Insulin 20 International Units
Serious: 5/37 (14%)
Deaths: 0/37
Intranasal Insulin 10 International Units
Serious: 3/33 (9%)
Deaths: 0/33
Placebo
Serious: 5/35 (14%)
Deaths: 0/35

Serious adverse events (10 terms)

ReactionSystemIntranasal Insulin 20 Inte…Intranasal Insulin 10 Inte…Placebo
Worsening of neurological symptomsNervous system disorders
Urinary Tract InfectionInfections and infestations
Perirectal abscessInfections and infestations
FallInjury, poisoning and procedural complications
Non-epileptic seizurePsychiatric disorders
Zoster ophthalmicusInfections and infestations
Small bowel obstructionGastrointestinal disorders
Chest painCardiac disorders
Multiple sclerosis relapseNervous system disorders
DizzinessNervous system disorders
Other adverse events (19 terms — click to expand)

ReactionSystemIntranasal Insulin 20 Inte…Intranasal Insulin 10 Inte…Placebo
HeadacheNervous system disorders
RhinorrheaRespiratory, thoracic and mediastinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders
PainGeneral disorders
DizzinessNervous system disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Upper respiratory infectionInfections and infestations
FractureInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
IrritabilityPsychiatric disorders
Dry mouthGastrointestinal disorders
PresyncopeNervous system disorders
NightmarePsychiatric disorders
FallInjury, poisoning and procedural complications
WeaknessMusculoskeletal and connective tissue disorders
Memory impairmentNervous system disorders
ParesthesiaNervous system disorders
DiarrheaGastrointestinal disorders

Most-reported serious reactions: Worsening of neurological symptoms, Urinary Tract Infection, Perirectal abscess, Fall, Non-epileptic seizure, Zoster ophthalmicus, Small bowel obstruction, Chest pain.

Data from ClinicalTrials.gov NCT02988401 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Non-Invasive Strategies for Nose-to-Brain Drug Delivery.
    Trevino JT, Quispe RC, Khan F, Novak V. · · 2020 · cited 59× · PMID 33505777
  2. Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations.
    Koo J, Lim C, Oh KT. · · 2024 · cited 57× · PMID 38414526 · DOI 10.2147/ijn.s439181
  3. The Nasal-Brain Drug Delivery Route: Mechanisms and Applications to Central Nervous System Diseases.
    Qiu Y, Huang S, Peng L, Yang L, et al · · 2025 · cited 18× · PMID 40487748 · DOI 10.1002/mco2.70213
  4. Intranasal insulin for improving cognitive function in multiple sclerosis.
    Newsome SD, Fitzgerald KC, Hughes A, Beier M, et al · · 2025 · cited 1× · PMID 40253245 · DOI 10.1016/j.neurot.2025.e00581
  5. Intranasal vs. Device-Assisted Drug Delivery: Advantages and Limitations for the Delivery of Biopharmaceuticals to the CNS.
    De Martini LB, Valori CF, Morrone M, Brambilla L, et al · · 2026 · PMID 42076135 · DOI 10.3390/pharmaceutics18040484
  6. The Potential of β-Synuclein-Specific Regulatory T Cell Therapy as a Treatment for Progressive Multiple Sclerosis.
    Osmond GE, John NA, Ting YT, Ooi JD. · · 2025 · PMID 41373685 · DOI 10.3390/ijms262311534

Verify or expand the search:

Other trials of Insulin

Trials testing the same drug.

Other recruiting trials for Multiple Sclerosis, Relapsing-Remitting

Currently open trials in the same condition.

Other Johns Hopkins University trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02988401.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing