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CompletedNCT01337986Updated Jan 30, 2020Results posted

Ampyra for Optic Neuritis in Multiple Sclerosis

A Phase 2/3 interventional study of Dalfampridine/Placebo and Placebo/Dalfampridine in Multiple Sclerosis and Optic Neuritis, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2020-01-30.

Sponsored by Washington University School of Medicine · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
53
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

Fifty subjects will be enrolled in this Phase II, investigator-initiated, randomized and blinded cross-over trial of dalfampridine of 8 weeks duration The study will test the hypothesis that dalfampridine, when administered to subjects with incomplete visual recovery after optic neuritis from MS, will result in symptomatic improvement in visual function. The study will consist of one screening/baseline visit, one visit during treatment with active drug, and one visit on placebo. After the baseline visit, subjects will be randomly assigned to receive study medication or placebo for the first three weeks, followed by a two week wash-out, and then treatment reallocation for the latter three weeks.

Read the detailed description

Optic neuritis (ON) is the presenting feature of multiple sclerosis (MS) in 15% of cases, and occurs over the disease course in 50% of patients.1-3 Vision remains a major concern for MS patients, as visual dysfunction leads to lower quality of life.4-6 Despite the high prevalence of ON in MS, treatment and management options remain limited. Although intravenous glucocorticoids are employed to aid recovery of an acute episode of ON, no convincing evidence supports their efficacy in altering the degree of long-term recovery.7 Although some individuals with ON can have a dramatic recovery from blindness, ON often impairs visual function permanently. In the Optic Neuritis Treatment Trial, 63% reported that vision had not returned to normal after 6 months, and 20% had vision worse than 20/20 after 5 years of follow-up.8, 9 Visual impairment creates difficulties at home and work, leading to decreased independence and impaired mobility within the community. Visual dysfunction in combination with MS impairments within cerebellar and proprioceptive systems can be particularly disabling.

Optic neuritis classically impairs one's ability to read print or a computer screen, to drive in bright or low light, and to appreciate colors and contrasts. Unfortunately, when optic neuritis results in lasting impairment, there are no pharmacologic therapies to restore vision. Low vision specialists may provide magnifying glasses, brighter lights, and advice to optimize the position of objects at home and in the workplace. Better treatment options are needed to improve visual function.

Ampyra (dalfampridine) is a potassium-channel antagonist, with a mechanism-of-action to improve nerve conduction in demyelinated axons, resulting in an electrophysiologic and clinical benefit.10-22 Demyelinated axons within the anterior visual pathway would be a prime and ideal target to study the effects of Ampyra. In fact, Stefoski et al demonstrated visual function benefit in an open-label study of IV 4-aminopyridine in 12 subjects.21 The optic nerves are a well-defined white-matter tract, commonly affected in MS, and with clear clinical outcome measures. In addition, visual evoked potentials (VEPs) can be included within the study design as a secondary endpoint, to confirm improved nerve conduction. Because VEPs are such a precise, reliable, and accepted measure of demyelination, the anterior visual pathway is the ideal in vivo human system to study the electro-physiologic effects of a therapeutic such as Ampyra.

Hypothesis 1: Dalfampridine treatment will improve visual function, measured by the 5% ETDRS contrast sensitivity chart, in subjects with long-term visual impairment secondary to optic neuritis from MS.

Hypothesis 2: Dalfampridine treatment will reduce visual evoked potential P100 latency following remote optic neuritis.

Hypothesis 3: Dalfampridine treatment will result in an improvement in secondary endpoints, including visual fields, high contrast visual acuity, color vision, and quality of life.

The study will be conducted at the Department of Neurology and Neurosurgery, Washington University School of Medicine, St. Louis, the institution at which Dr. Naismith is based. The MS patients will come from the 1800 active MS patients in our clinic and the 3500 in the St. Louis area.

Fifty subjects will be enrolled in this Phase II, investigator-initiated, randomized and blinded cross-over trial of dalfampridine of 8 weeks duration (Table 1). The study will test the hypothesis that dalfampridine, when administered to subjects with incomplete visual recovery after optic neuritis from MS, will result in symptomatic improvement in visual function. The study will consist of one screening/baseline visit, one visit during treatment with active drug, and one visit on placebo. After the baseline visit, subjects will be randomly assigned to receive study medication or placebo for the first three weeks, followed by a two week wash-out, and then treatment reallocation for the latter three weeks.

02

Conditions studied

  • Multiple Sclerosis
  • Optic Neuritis

Keywords

  • Multiple Sclerosis
  • Optic Neuritis
  • Ampyra
  • Dalfampridine
  • Fampridine
  • Remote Optic Neuritis
  • Contrast Sensitivity
  • Treatment
03

In context

Multiple Sclerosis

3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.

This study's enrollment of 53 is close to the median of 50 across 2,201 interventional studies indexed under Multiple Sclerosis.

Browse Multiple Sclerosis studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,803 studies on the registry; 271 are open to participants now.

Of its 329 completed or terminated interventional studies of FDA-regulated products, 216 (66%) have results posted.

Browse Washington University School of Medicine studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. At least one previous clinical episode of optic neuritis,
  2. the last episode of ON must have occurred at least 12 months prior to study entry,
  3. clinically definite MS, defined by the revised McDonald criteria, 23
  4. ages 18-70,
  5. visual acuity greater than or equal to 20/30
  6. must be able to read at least 2 of the 5 letters on the top line of the 5% ETDRS chart (logMAR 0.96) at 3 meters, 2 meters or 1 meter, and
  7. must have sufficient cognitive function to understand the consent process and to reliably perform all clinical assessments

Exclusion criteria

Exclusion criteria are:

  1. Any ophthalmologic condition, other than ON, which can affect vision, including nystagmus in primary position of gaze,
  2. history of seizures or spells with altered level of consciousness,
  3. pregnancy or breast feeding,
  4. an MS exacerbation or use of within 3 months of entry,
  5. a history of moderate to severe renal insufficiency,
  6. previous use of 4-aminopyridine, in any formulation, in the prior 4 weeks.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Participant)
Enrollment
53 participants (actual)

Study arms

  • Active comparator
    Group B: Dalfampridine First

    Dalfampridine/Placebo: Weeks 1-3: Dalfampridine 10mg (1 tablet) every 12 hours for 3 weeks. Weeks 4-5: 2 weeks of wash-out. Weeks 5-8: Placebo (sugar pill) 1 tablet every 12 hours for 3 weeks.

    Drug: Dalfampridine/Placebo

  • Active comparator
    Group A: Dalfampridine Second

    Placebo/Dalfampridine: Weeks 1-3: Placebo (sugar pill) 1 tablet every 12 hours for 3 weeks. Weeks 4-5: 2 weeks of wash-out. Weeks 6-8: Dalfampridine 10mg (1 tablet) every 12 hours for 3 weeks

    Drug: Placebo/Dalfampridine

Interventions

  • DrugDalfampridine/Placebo

    Weeks 1-3: Dalfampridine 10mg (1 tablet) every 12 hours for 3 weeks. Weeks 4-5: 2 weeks of wash-out. Weeks 5-8: Placebo (sugar pill) 1 tablet every 12 hours for 3 weeks.

    Also known as: Ampyra (R), Fampridine

  • DrugPlacebo/Dalfampridine

    Weeks 1-3: Placebo (sugar pill) 1 tablet every 12 hours for 3 weeks. Weeks 4-5: 2 weeks of wash-out. Weeks 6-8: Dalfampridine 10mg (1 tablet) every 12 hours for 3 weeks.

    Also known as: Ampyra (R), Fampridine

06

What researchers measure

Primary outcomes

  1. Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores

    Per Protocol Analysis to assess differences in EDTRS 5% Contrast Sensitivity (LogMAR) Scores at visits 2 and 3 Relative to Visit 1 on patients taking Dalfampridine vs Placebo.

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  2. Efficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity

    Per Protocol Analysis to assess difference in number of letters on the EDTRS 5% Contrast Sensitivity (LogMAR) Chart scores at visits 2 and 3 Relative to Visit 1

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  3. Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1

    Intent to treat analysis of treatment effect in primary endpoint EDTRS 5% Contrast Sensitivity. Improvement from baseline scores.

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  4. Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity

    Intent to treat analysis of treatment effect in primary endpoint EDTRS 5% Contrast Sensitivity. Change in the number of letters able to read while on Dalfampridine and Placebo relative to their baseline scores.

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Secondary outcomes

  1. Percentage of Eyes That Improved by 2 Lines (10 Letters) on the Sloan 5% Contrast Sensitivity Chart

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  2. Percentage of Eyes That Improved by One-line (5 Letters)

    Percentage of eyes that improved by one-line (5 letters) on the 5% contrast sensitivity chart

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  3. Visual Evoked Potential P100 Latency Per Treatment Arm

    Visual evoked potential 60min P100 latency on dalfampridine vs. placebo.

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  4. Odds Ratio Quartile of Visual Field Index

    The Visual Field Index (VFI) is a global index that assigns a number between 1% to 100% based on an aggregate percentage of visual function, with 100% being a perfect age-adjusted visual field. Probability of falling in the best quartile for visual field (VFI) measures (Q1), relative to the three next quartiles for worse VFIs (Q2-4), while on Dalfampridine vs Placebo. Due to the clustered observations at different times in a cross-over design, the visual field data is not suited to a normal theory model and should not be expressed as a continuous variable. Thus, a categorical model that uses a multinomial distribution for measurement of 4 categories was selected for proper statistical modeling, with results expressed as odds ratios.

    Time frame: Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - post intervention 1) and Visit 3 (Week 8 - post intervention 2)

  5. Changes in Color Vision Total Error Score From Baseline Based Upon the Farnsworth Munsell Hue 100 Sort Test (FM100).

    Dalfampridine will change color vision Total Error Scores from baseline on the Farnsworth Munsell 100 Hue Sort Test. Farnsworth Munsell 100 Hue Test requires placing 100 color palettes in the correct order based upon color hue. Scores are determined by the frequency and severity of any displacement in the correct order. One error equates to one misplaced hue, by one step or position. An error score greater than 500 indicates virtually no color discrimination. An error score of 0 indicates no errors in ordering the hues. A Total Error Score of 0 to 128 could be seen in a normal population.

    Time frame: Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - postintervention 1) and Visit 3 (Week 8 - post intervention 2)

  6. Dalfampridine Effect on Quality of Life Change From Baseline.

    Dalfampridine treatment will result in change in quality of life. The National Eye Institute Visual Function Questionnaire consists of 25 questions characterizing visual function at home and in the community. Score ranges from 100 (best) to 0 (worst).

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  7. Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1

    Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1 on Dalfampridine vs Placebo. Pelli-Robson is scored based upon the numbers read on the chart converted to LogMAR units. The scale is 0.00 (worst) to 2.35 (best).

    Time frame: Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

07

Results

Posted Jan 30, 2020
Limitations and caveats
Pilot study with relatively small number of patients compared to a phase III study. Cross-over design may be inferior to placebo-controlled parallel cohort study.

Participant flow

Subjects were recruited from the John L Trotter Multiple Sclerosis (MS) Clinic at Washington University and through email blasts from the Gateway (St. Louis) MS Chapter. 53 participants meet the pre-screening criteria and signed an informed consent to be screened for the study.

Participant flow — Overall Study
MilestoneGroup B: Dalfampridine/PlaceboGroup A: Placebo/Dalfampridine
Started2323
Completed2018
Not completed35
Withdrew: Adverse event22
Withdrew: Lost to follow-up10
Withdrew: Protocol violation03

Outcome measures

PrimaryEfficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores

Per Protocol Analysis to assess differences in EDTRS 5% Contrast Sensitivity (LogMAR) Scores at visits 2 and 3 Relative to Visit 1 on patients taking Dalfampridine vs Placebo.

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Mean · LogMAR Score
Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores
LogMAR ScoreGroup B: DalfampridineGroup B: PlaceboGroup A: PlaceboGroup A: Dalfampridine
Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores-0.04 ± 0.02-0.06 ± 0.02-0.08 ± 0.02-0.06 ± 0.02
Statistical analysis
  • Group B: Dalfampridine vs Group B: Placebo vs Group A: Placebo vs Group A: Dalfampridine · Mixed Models Analysis · p = 0.84
  • Group B: Dalfampridine vs Group B: Placebo vs Group A: Placebo vs Group A: Dalfampridine · Mixed Models Analysis · p = .29
PrimaryEfficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity

Per Protocol Analysis to assess difference in number of letters on the EDTRS 5% Contrast Sensitivity (LogMAR) Chart scores at visits 2 and 3 Relative to Visit 1

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Mean · letters
Efficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
lettersGroup B: DalfampridineGroup B: PlaceboGroup A: PlaceboGroup A: Dalfampridine
Efficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity2 ± 12 ± 14 ± 13 ± 1
PrimaryDifference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1

Intent to treat analysis of treatment effect in primary endpoint EDTRS 5% Contrast Sensitivity. Improvement from baseline scores.

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Mean · 5% Contrast LogMAR Score
Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1
5% Contrast LogMAR ScoreDalfampridinePlacebo
Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 10.06 ± 0.020.05 ± 0.02
Statistical analysis
  • Dalfampridine vs Placebo · Mixed Models Analysis · p = .64 · Mean difference (final values): 0.008
  • Dalfampridine vs Placebo · Mixed Models Analysis · p = 0.11
SecondaryPercentage of Eyes That Improved by 2 Lines (10 Letters) on the Sloan 5% Contrast Sensitivity Chart
Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Number · Percentages of eyes that improved
Percentage of Eyes That Improved by 2 Lines (10 Letters) on the Sloan 5% Contrast Sensitivity Chart
Percentages of eyes that improvedDalfampridinePlaceboBothNone
Percentage of Eyes That Improved by 2 Lines (10 Letters) on the Sloan 5% Contrast Sensitivity Chart9.7 (4.0 to 19.0)11.1 (4.9 to 20.7)11.1 (4.9 to 20.7)68.1 (56.0 to 78.6)
Statistical analysis
  • Dalfampridine vs Placebo vs Both vs None · Regression, Logistic · p = 0.93
SecondaryPercentage of Eyes That Improved by One-line (5 Letters)

Percentage of eyes that improved by one-line (5 letters) on the 5% contrast sensitivity chart

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Number · Percent of Eyes
Percentage of Eyes That Improved by One-line (5 Letters)
Percent of EyesDalfampridinePlaceboBothNeither
Percentage of Eyes That Improved by One-line (5 Letters)11.1 (4.9 to 20.7)15.3 (7.9 to 25.7)37.5 (26.4 to 49.7)36.1 (25.1 to 48.3)
Statistical analysis
  • Dalfampridine vs Placebo vs Both · Regression, Logistic · p = .34
SecondaryVisual Evoked Potential P100 Latency Per Treatment Arm

Visual evoked potential 60min P100 latency on dalfampridine vs. placebo.

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Mean · milliseconds
Visual Evoked Potential P100 Latency Per Treatment Arm
millisecondsDalfampridinePlacebo
Visual Evoked Potential P100 Latency Per Treatment Arm121.6 ± 2.4120.2 ± 2.4
SecondaryOdds Ratio Quartile of Visual Field Index

The Visual Field Index (VFI) is a global index that assigns a number between 1% to 100% based on an aggregate percentage of visual function, with 100% being a perfect age-adjusted visual field. Probability of falling in the best quartile for visual field (VFI) measures (Q1), relative to the three next quartiles for worse VFIs (Q2-4), while on Dalfampridine vs Placebo. Due to the clustered observations at different times in a cross-over design, the visual field data is not suited to a normal theory model and should not be expressed as a continuous variable. Thus, a categorical model that uses a multinomial distribution for measurement of 4 categories was selected for proper statistical modeling, with results expressed as odds ratios.

Time frame:
Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - post intervention 1) and Visit 3 (Week 8 - post intervention 2)
Reported as:
Mean · Visual Field Index % of normal vision
Odds Ratio Quartile of Visual Field Index
Visual Field Index % of normal visionDalfampridine Then PlaceboPlacebo Then Dalfampridine
Baseline (Visit 1)77.53 ± 29.8485.38 ± 86.65
Post Intervention 1 (Visit 2)78.50 ± 28.3086.65 ± 22.64
Post Intervention 2 (Visit 3)79.71 ± 28.5786.00 ± 22.75
Statistical analysis
  • Dalfampridine Then Placebo vs Placebo Then Dalfampridine · Regression, Logistic · p = 0.04 (Probability of being in the lowest quartile for Visual Field Index deficits.) · Odds ratio (or): 1.46 · 95% CI 1.02 to 2.10Odds Ratio for Visual Field Index
SecondaryChanges in Color Vision Total Error Score From Baseline Based Upon the Farnsworth Munsell Hue 100 Sort Test (FM100).

Dalfampridine will change color vision Total Error Scores from baseline on the Farnsworth Munsell 100 Hue Sort Test. Farnsworth Munsell 100 Hue Test requires placing 100 color palettes in the correct order based upon color hue. Scores are determined by the frequency and severity of any displacement in the correct order. One error equates to one misplaced hue, by one step or position. An error score greater than 500 indicates virtually no color discrimination. An error score of 0 indicates no errors in ordering the hues. A Total Error Score of 0 to 128 could be seen in a normal population.

Time frame:
Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - postintervention 1) and Visit 3 (Week 8 - post intervention 2)
Reported as:
Mean · FM100 Total Error Score
Changes in Color Vision Total Error Score From Baseline Based Upon the Farnsworth Munsell Hue 100 Sort Test (FM100).
FM100 Total Error ScoreDalfampridinePlacebo
Changes in Color Vision Total Error Score From Baseline Based Upon the Farnsworth Munsell Hue 100 Sort Test (FM100).-13.0 (-15.0 to -11.0)-10.6 (-28.3 to -7.1)
Statistical analysis
  • Dalfampridine vs Placebo · Regression, Logistic · p = 0.94
SecondaryDalfampridine Effect on Quality of Life Change From Baseline.

Dalfampridine treatment will result in change in quality of life. The National Eye Institute Visual Function Questionnaire consists of 25 questions characterizing visual function at home and in the community. Score ranges from 100 (best) to 0 (worst).

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Median · NEI VFQ percentage
Dalfampridine Effect on Quality of Life Change From Baseline.
NEI VFQ percentageDalfampridinePlacebo
Dalfampridine Effect on Quality of Life Change From Baseline.0 (-40.0 to 30.0)0 (-35.0 to 302.5)
Statistical analysis
  • Dalfampridine vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.39
SecondaryDifference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1

Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1 on Dalfampridine vs Placebo. Pelli-Robson is scored based upon the numbers read on the chart converted to LogMAR units. The scale is 0.00 (worst) to 2.35 (best).

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Mean · units on a scale
Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1
units on a scaleDalfampridinePlacebo
Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 10.07 ± 0.020.06 ± 0.02
Statistical analysis
  • Dalfampridine vs Placebo · Regression, Linear · p = 0.72
PrimaryChange From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity

Intent to treat analysis of treatment effect in primary endpoint EDTRS 5% Contrast Sensitivity. Change in the number of letters able to read while on Dalfampridine and Placebo relative to their baseline scores.

Time frame:
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Reported as:
Mean · letters
Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
lettersDalfampridinePlacebo
Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity3 ± 12.5 ± 1

Adverse events

Collected over 8 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dalfampridine0/46 (0%)0/46 (0%)4/46 (8.7%)
Placebo0/46 (0%)0/46 (0%)0/46 (0%)
Most frequent other events
Most frequent other events
EventDalfampridinePlacebo
DizzinessNervous system disorders4/460/46

Baseline characteristics

All patients that were randomized and included in the per-protocol analysis (compliantly completed 3 visits on assigned treatment).

Age, Categorical
Age, Categorical(Participants)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
<=18 years000
Between 18 and 65 years181735
>=65 years213
Age, Continuous
Age, Continuous(years)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
Mean44.5 ± 10.750.7 ± 10.247.6 ± 10.5
Sex: Female, Male
Sex: Female, Male(Participants)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
Female141428
Male6410
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American459
White161329
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
United States201838
MS Subtype
MS Subtype(participants)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
Relapsing Remitting MS (RRMS)171532
Secondary Progressive MS (SPMS)336
Clinical Episodes of ON
Clinical Episodes of ON(Number of episodes)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
Median1 (1 to 4)1 (1 to 4)1 (1 to 4)
Baseline 5% Sloan Chart
Baseline 5% Sloan Chart(Number of Letters)Group B: Dalfampridine/PlaceboGroup A: Placebo/DalfampridineTotal
Median22 (2 to 46)20 (2 to 45)21 (2 to 46)
08

Study locations

1 site
  • Washington University (John L. Trotter MS Center)
    Saint Louis, Missouri 63110, United States
09

References and documents

Publications

  • Frohman EM, Frohman TC, Zee DS, McColl R, Galetta S. The neuro-ophthalmology of multiple sclerosis. Lancet Neurol. 2005 Feb;4(2):111-21. doi: 10.1016/S1474-4422(05)00992-0. PubMed 15664543 ↗
  • Arnold AC. Evolving management of optic neuritis and multiple sclerosis. Am J Ophthalmol. 2005 Jun;139(6):1101-8. doi: 10.1016/j.ajo.2005.01.031. PubMed 15953446 ↗
  • Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med. 2006 Mar 23;354(12):1273-80. doi: 10.1056/NEJMcp053247. No abstract available. PubMed 16554529 ↗
  • Ma SL, Shea JA, Galetta SL, Jacobs DA, Markowitz CE, Maguire MG, Balcer LJ. Self-reported visual dysfunction in multiple sclerosis: new data from the VFQ-25 and development of an MS-specific vision questionnaire. Am J Ophthalmol. 2002 May;133(5):686-92. doi: 10.1016/s0002-9394(02)01337-5. PubMed 11992867 ↗
  • Noble J, Forooghian F, Sproule M, Westall C, O'Connor P. Utility of the National Eye Institute VFQ-25 questionnaire in a heterogeneous group of multiple sclerosis patients. Am J Ophthalmol. 2006 Sep;142(3):464-8. doi: 10.1016/j.ajo.2006.04.051. PubMed 16935592 ↗
  • Mowry EM, Loguidice MJ, Daniels AB, Jacobs DA, Markowitz CE, Galetta SL, Nano-Schiavi ML, Cutter GR, Maguire MG, Balcer LJ. Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity. J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):767-72. doi: 10.1136/jnnp.2008.165449. Epub 2009 Feb 23. PubMed 19240050 ↗
  • Beck RW, Cleary PA, Anderson MM Jr, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27;326(9):581-8. doi: 10.1056/NEJM199202273260901. PubMed 1734247 ↗
  • Visual function 5 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. The Optic Neuritis Study Group. Arch Ophthalmol. 1997 Dec;115(12):1545-52. PubMed 9400788 ↗
  • Cleary PA, Beck RW, Bourque LB, Backlund JC, Miskala PH. Visual symptoms after optic neuritis. Results from the Optic Neuritis Treatment Trial. J Neuroophthalmol. 1997 Mar;17(1):18-23; quiz 24-8. doi: 10.1016/s0002-9394(14)70814-1. PubMed 9093956 ↗
  • Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F203 Investigators. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8. doi: 10.1016/S0140-6736(09)60442-6. PubMed 19249634 ↗
  • Fujihara K, Miyoshi T. The effects of 4-aminopyridine on motor evoked potentials in multiple sclerosis. J Neurol Sci. 1998 Jul 15;159(1):102-6. doi: 10.1016/s0022-510x(98)00143-9. PubMed 9700711 ↗
  • Schwid SR, Petrie MD, McDermott MP, Tierney DS, Mason DH, Goodman AD. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Neurology. 1997 Apr;48(4):817-21. doi: 10.1212/wnl.48.4.817. PubMed 9109861 ↗
  • Davis FA, Stefoski D, Quandt FN. Mechanism of action of 4-aminopyridine in the symptomatic treatment of multiple sclerosis. Ann Neurol. 1995 May;37(5):684. doi: 10.1002/ana.410370524. No abstract available. PubMed 7755367 ↗
  • Bever CT Jr, Young D, Anderson PA, Krumholz A, Conway K, Leslie J, Eddington N, Plaisance KI, Panitch HS, Dhib-Jalbut S, et al. The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology. 1994 Jun;44(6):1054-9. doi: 10.1212/wnl.44.6.1054. PubMed 8208399 ↗
  • Polman CH, Bertelsmann FW, van Loenen AC, Koetsier JC. 4-aminopyridine in the treatment of patients with multiple sclerosis. Long-term efficacy and safety. Arch Neurol. 1994 Mar;51(3):292-6. doi: 10.1001/archneur.1994.00540150090022. PubMed 8129642 ↗
  • van Diemen HA, Polman CH, van Dongen MM, Nauta JJ, Strijers RL, van Loenen AC, Bertelsmann FW, Koetsier JC. 4-Aminopyridine induces functional improvement in multiple sclerosis patients: a neurophysiological study. J Neurol Sci. 1993 Jun;116(2):220-6. doi: 10.1016/0022-510x(93)90329-w. PubMed 8336169 ↗
  • van Diemen HA, Polman CH, van Dongen TM, van Loenen AC, Nauta JJ, Taphoorn MJ, van Walbeek HK, Koetsier JC. The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. Ann Neurol. 1992 Aug;32(2):123-30. doi: 10.1002/ana.410320203. PubMed 1510353 ↗
  • Stefoski D, Davis FA, Fitzsimmons WE, Luskin SS, Rush J, Parkhurst GW. 4-Aminopyridine in multiple sclerosis: prolonged administration. Neurology. 1991 Sep;41(9):1344-8. doi: 10.1212/wnl.41.9.1344. PubMed 1891078 ↗
  • Polman CH, van Diemen HA, van Dongen MM, Koetsier JC, van Loenen AC, van Walbeek HK. 4-Aminopyridine in multiple sclerosis. Ann Neurol. 1990 Oct;28(4):589. doi: 10.1002/ana.410280421. No abstract available. PubMed 2082971 ↗
  • Davis FA, Stefoski D, Rush J. Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. Ann Neurol. 1990 Feb;27(2):186-92. doi: 10.1002/ana.410270215. PubMed 2317014 ↗
  • Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. doi: 10.1002/ana.20703. PubMed 16283615 ↗
  • Jones RE, Heron JR, Foster DH, Snelgar RS, Mason RJ. Effects of 4-aminopyridine in patients with multiple sclerosis. J Neurol Sci. 1983 Aug-Sep;60(3):353-62. doi: 10.1016/0022-510x(83)90145-4. PubMed 6631441 ↗
  • Vollmer T, Henney HR 3rd. Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I-II, open-label trial. Clin Ther. 2009 Oct;31(10):2206-14. doi: 10.1016/j.clinthera.2009.10.008. PubMed 19922891 ↗
  • Vollmer T, Blight AR, Henney HR 3rd. Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study. Clin Ther. 2009 Oct;31(10):2215-23. doi: 10.1016/j.clinthera.2009.10.007. PubMed 19922892 ↗
  • Beck RW, Ruchman MC, Savino PJ, Schatz NJ. Contrast sensitivity measurements in acute and resolved optic neuritis. Br J Ophthalmol. 1984 Oct;68(10):756-9. doi: 10.1136/bjo.68.10.756. PubMed 6477856 ↗
  • Trobe JD, Beck RW, Moke PS, Cleary PA. Contrast sensitivity and other vision tests in the optic neuritis treatment trial. Am J Ophthalmol. 1996 May;121(5):547-53. doi: 10.1016/s0002-9394(14)75429-7. PubMed 8610798 ↗
  • Farnsworth D. The Farnsworth-Munsell 100-hue and dichotomous tests for color vision. J Opt Soc Am 1943;33:568-574.
  • Naismith RT, Tutlam NT, Xu J, Klawiter EC, Shepherd J, Trinkaus K, Song SK, Cross AH. Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis. Neurology. 2009 Mar 24;72(12):1077-82. doi: 10.1212/01.wnl.0000345042.53843.d5. PubMed 19307541 ↗
  • Naismith RT, Tutlam NT, Xu J, Shepherd JB, Klawiter EC, Song SK, Cross AH. Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis. Neurology. 2009 Jul 7;73(1):46-52. doi: 10.1212/WNL.0b013e3181aaea32. PubMed 19564583 ↗
  • Naismith RT, Xu J, Tutlam NT, Trinkaus K, Cross AH, Song SK. Radial diffusivity in remote optic neuritis discriminates visual outcomes. Neurology. 2010 May 25;74(21):1702-10. doi: 10.1212/WNL.0b013e3181e0434d. PubMed 20498438 ↗
  • Naismith RT, Xu J, Tutlam NT, Scully PT, Trinkaus K, Snyder AZ, Song SK, Cross AH. Increased diffusivity in acute multiple sclerosis lesions predicts risk of black hole. Neurology. 2010 May 25;74(21):1694-701. doi: 10.1212/WNL.0b013e3181e042c4. Erratum In: Neurology. 2010 Sep 7;75(10):938. PubMed 20498437 ↗
  • Naismith RT, Xu J, Tutlam NT, Snyder A, Benzinger T, Shimony J, Shepherd J, Trinkaus K, Cross AH, Song SK. Disability in optic neuritis correlates with diffusion tensor-derived directional diffusivities. Neurology. 2009 Feb 17;72(7):589-94. doi: 10.1212/01.wnl.0000335766.22758.cd. Epub 2008 Dec 10. PubMed 19073948 ↗
  • Naismith RT, Shepherd JB, Weihl CC, Tutlam NT, Cross AH. Acute and bilateral blindness due to optic neuropathy associated with copper deficiency. Arch Neurol. 2009 Aug;66(8):1025-7. doi: 10.1001/archneurol.2009.70. PubMed 19667226 ↗
  • Vanden Bosch ME, Wall M. Visual acuity scored by the letter-by-letter or probit methods has lower retest variability than the line assignment method. Eye (Lond). 1997;11 ( Pt 3):411-7. doi: 10.1038/eye.1997.87. PubMed 9373488 ↗
  • Acorda Therapeutics. AMPRYA package insert (2010).

Individual participant data

Plan to share: No

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 30, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01337986
Lead sponsor
Washington University School of Medicine
Collaborators
Acorda Therapeutics
Responsible party
Sponsor
First posted
Apr 19, 2011
Start date
May 2011
Primary completion
Dec 2013
Completion
Dec 2013
Results posted
Jan 30, 2020
Last update
Jan 30, 2020

Study contacts

Robert T Naismith, MD
principal investigator · Washington University School of Medicine

Oversight

Data monitoring committee
No
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