NCT01337986

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
53

participants targeted

Target at P25-P50 for phase_2 multiple-sclerosis

Timeline
Completed

Started May 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 13, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 19, 2011

Completed
12 days until next milestone

Study Start

First participant enrolled

May 1, 2011

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
6.2 years until next milestone

Results Posted

Study results publicly available

January 30, 2020

Completed
Last Updated

January 30, 2020

Status Verified

January 1, 2020

Enrollment Period

2.6 years

First QC Date

April 13, 2011

Results QC Date

May 4, 2016

Last Update Submit

January 23, 2020

Conditions

Multiple SclerosisOptic Neuritis

Keywords

Multiple SclerosisOptic NeuritisAmpyraDalfampridineFampridineRemote Optic NeuritisContrast SensitivityTreatment

Outcome Measures

Primary Outcomes (4)

  • 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.

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  • 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

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  • 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.

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  • 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.

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

Secondary Outcomes (7)

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

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

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

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  • Visual Evoked Potential P100 Latency Per Treatment Arm

    Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)

  • Odds Ratio Quartile of Visual Field Index

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

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

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

  • +2 more secondary outcomes

Study Arms (2)

Group B: Dalfampridine First

ACTIVE COMPARATOR

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

Group A: Dalfampridine Second

ACTIVE COMPARATOR

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

Dalfampridine/PlaceboDRUG

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
Group B: Dalfampridine First
Placebo/DalfampridineDRUG

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
Group A: Dalfampridine Second

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • At least one previous clinical episode of optic neuritis,
  • the last episode of ON must have occurred at least 12 months prior to study entry,
  • clinically definite MS, defined by the revised McDonald criteria, 23
  • ages 18-70,
  • visual acuity greater than or equal to 20/30
  • 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
  • must have sufficient cognitive function to understand the consent process and to reliably perform all clinical assessments

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University (John L. Trotter MS Center)

St Louis, Missouri, 63110, United States

Location

Related Publications (35)

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  • 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.

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  • 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.

    PMID: 1734247BACKGROUND

  • 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.

    PMID: 9400788BACKGROUND

  • 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.

    PMID: 9093956BACKGROUND

  • 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.

    PMID: 19249634BACKGROUND

  • 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.

    PMID: 9700711BACKGROUND

  • 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.

    PMID: 9109861BACKGROUND

  • 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.

    PMID: 7755367BACKGROUND

  • 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.

    PMID: 8208399BACKGROUND

  • 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.

    PMID: 8129642BACKGROUND

  • 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.

    PMID: 8336169BACKGROUND

  • 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.

    PMID: 1510353BACKGROUND

  • 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.

    PMID: 1891078BACKGROUND

  • 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.

    PMID: 2082971BACKGROUND

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    PMID: 2317014BACKGROUND

  • 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.

    PMID: 16283615BACKGROUND

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    BACKGROUND

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  • Acorda Therapeutics. AMPRYA package insert (2010).

    BACKGROUND

MeSH Terms

Conditions

Multiple SclerosisOptic Neuritis

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesOptic Nerve DiseasesCranial Nerve DiseasesEye Diseases

Intervention Hierarchy (Ancestors)

AminopyridinesAminesOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

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.

Results Point of Contact

Title
Robert Naismith, MD
Organization
Washington Univerisity St. Louis
naismithr@wustl.edu
314-747-5576

Study Officials

  • Robert T Naismith, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 13, 2011

First Posted

April 19, 2011

Study Start

May 1, 2011

Primary Completion

December 1, 2013

Study Completion

December 1, 2013

Last Updated

January 30, 2020

Results First Posted

January 30, 2020

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)