Ampyra for Optic Neuritis in Multiple Sclerosis
Dalfampridine After Optic Neuritis to Improve Visual Function in Multiple Sclerosis
What it found
The main measure did not show a significant benefit.
| Measure | Estimate | 95% CI | p |
|---|---|---|---|
| Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1 | 0.11 | ||
| Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores | .29 | ||
| Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1 | Mean Difference (Final Values) 0.008 | .64 | |
| Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores | 0.84 |
Statistical analysis as posted on ClinicalTrials.gov.
What was tested
Placebo
- Dalfampridine/Placebo
- Placebo/Dalfampridine
Results by group
Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Group B: Dalfampridine | -0.04 LogMAR Score | 0.02 (Standard Deviation) | 30 |
| Group B: Placebo | -0.06 LogMAR Score | 0.02 (Standard Deviation) | 30 |
| Group A: Placebo | -0.08 LogMAR Score | 0.02 (Standard Deviation) | 29 |
| Group A: Dalfampridine | -0.06 LogMAR Score | 0.02 (Standard Deviation) | 29 |
Group B: Dalfampridine
Group B: Placebo
Group A: Placebo
Group A: Dalfampridine
p = 0.84
Efficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Group B: Dalfampridine | 2 letters | 1 (Standard Deviation) | 30 |
| Group B: Placebo | 2 letters | 1 (Standard Deviation) | 30 |
| Group A: Placebo | 4 letters | 1 (Standard Deviation) | 29 |
| Group A: Dalfampridine | 3 letters | 1 (Standard Deviation) | 29 |
Group B: Dalfampridine
Group B: Placebo
Group A: Placebo
Group A: Dalfampridine
Difference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Dalfampridine | 0.06 5% Contrast LogMAR Score | 0.02 (Standard Deviation) | 46 |
| Placebo | 0.05 5% Contrast LogMAR Score | 0.02 (Standard Deviation) | 46 |
Dalfampridine
Placebo
p = .64; Mean Difference (Final Values) 0.008
Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Dalfampridine | 3 letters | 1 (Standard Deviation) | 46 |
| Placebo | 2.5 letters | 1 (Standard Deviation) | 46 |
Dalfampridine
Placebo
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Dalfampridine | 46 | 0 (0.0%) | 0 |
| Placebo | 46 | 0 (0.0%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Efficacy of Dalfampridine on Visual Function by Early Diabetic Treatment Retinopathy Study (EDTRS) 5% Contrast Sensitivity Scores
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
VisionEfficacy of Dalfampridine on Visual Function Assessed by Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
VisionDifference in EDTRS 5% Contrast Sensitivity (LogMAR Score) at Visits 2 and 3 Relative to Visit 1
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Change From Baseline in Raw Letters by EDTRS 5% Contrast Sensitivity
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Other measures (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)
Myelin repairOdds 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)
VisionChanges 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)
VisionDalfampridine Effect on Quality of Life Change From Baseline.
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
VisionQuality of life (reported by participants)Difference in Pelli- Robson Score at Visits 2 and 3 Relative to Visit 1
Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8)
Who could take part
MS (type not specified) · 18 to 55
Show the full criteria
Inclusion criteria
Inclusion criteria are: 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 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 glucocorticoids 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.
Exclusion criteria
Not separately supplied in the registry.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
Background
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.Background
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.Background
Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med. 2006 Mar 23;354(12):1273-80. doi: 10.1056/NEJMcp053247. No abstract available.Background
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.Background
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.Background
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.Background
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.Background
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.Background
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.Background
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.
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History
Started
May 2011
Main results due
Dec 2013
Finished
Dec 2013
Results posted
Jan 2020