Ampyra for Optic Neuritis in MS

This study has been completed.

Sponsor:

Collaborator:

Acorda Therapeutics

Information provided by (Responsible Party):

Robert Naismith, Washington University School of Medicine

ClinicalTrials.gov Identifier:

NCT01337986

First received: April 13, 2011

Last updated: February 14, 2014

Last verified: February 2014

History of Changes

Purpose

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.

Condition	Intervention	Phase
Multiple Sclerosis Optic Neuritis	Drug: Dalfampridine/Placebo Drug: Placebo/Dalfampridine	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Dalfampridine After Optic Neuritis to Improve Visual Function in Multiple Sclerosis

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Dalfampridine

Genetic and Rare Diseases Information Center resources: Optic Neuritis

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

Efficacy of Dalfampridine on visual function (contrast sensitivity). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Dalfampridine reduce visual evoked potential P100 latency. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Dalfampridine treatment will reduce visual evoked potential P100 latency following remote optic neuritis.
Dalfampridine improvement in other vision testing (acuity, color, and fields). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Dalfampridine treatment will result in an improvement in visual fields, high contrast visual acuity, and color vision.
Dalfampridine affect on quality of life. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Dalfampridine treatment will result in an improvement quality of life.


Enrollment:	53
Study Start Date:	May 2011
Study Completion Date:	December 2013
Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group A: Dalfampridine/Placebo	Drug: 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. Other Names: Ampyra (R) Fampridine
Active Comparator: Group B: Placebo/Dalfampridine	Drug: 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. Other Names: Ampyra (R) Fampridine

Show Detailed Description

Eligibility


Ages Eligible for Study:	18 Years to 55 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria are:

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

Exclusion criteria are:

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01337986

Locations


United States, Missouri
Washington University (John L. Trotter MS Center)
St. Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Acorda Therapeutics

Investigators


Principal Investigator:	Robert T Naismith, MD	Washington University School of Medicine

More Information

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. Review.

Arnold AC. Evolving management of optic neuritis and multiple sclerosis. Am J Ophthalmol. 2005 Jun;139(6):1101-8. Review.

Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med. 2006 Mar 23;354(12):1273-80. Review.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Davis FA, Stefoski D, Rush J. Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. Ann Neurol. 1990 Feb;27(2):186-92.

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. Review.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Acorda Therapeutics. AMPRYA package insert (2010).


Responsible Party:	Robert Naismith, Assistant Professor of Neurology, Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT01337986 History of Changes
Other Study ID Numbers:	Ampyra Vision 2011 RTN WU HRPO# : 201104126
Study First Received:	April 13, 2011
Last Updated:	February 14, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:


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

Additional relevant MeSH terms:


Sclerosis Multiple Sclerosis Neuritis Optic Neuritis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases	Immune System Diseases Peripheral Nervous System Diseases Neuromuscular Diseases Optic Nerve Diseases Cranial Nerve Diseases Eye Diseases 4-Aminopyridine Potassium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016

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