Multiple Sclerosis Clinical Trial
Official title:
Dalfampridine After Optic Neuritis to Improve Visual Function in Multiple Sclerosis
Verified date | January 2020 |
Source | Washington University School of Medicine |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 53 |
Est. completion date | December 2013 |
Est. primary completion date | December 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
United States | Washington University (John L. Trotter MS Center) | Saint Louis | Missouri |
Lead Sponsor | Collaborator |
---|---|
Washington University School of Medicine | Acorda Therapeutics |
United States,
Acorda Therapeutics. AMPRYA package insert (2010).
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* Note: There are 35 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | 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) | |
Primary | 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) | |
Primary | 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 | 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) | ||
Secondary | 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 | Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8) | |
Secondary | Visual Evoked Potential P100 Latency Per Treatment Arm | Visual evoked potential 60min P100 latency on dalfampridine vs. placebo. | Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8) | |
Secondary | 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. |
Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - post intervention 1) and Visit 3 (Week 8 - post intervention 2) | |
Secondary | 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. | Visit 1 (Week 0 - baseline), Visit 2 (Week 3 - postintervention 1) and Visit 3 (Week 8 - post intervention 2) | |
Secondary | 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). | Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8) | |
Secondary | 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). | Visit 1 (Week 0), Visit 2 (Week 3) and Visit 3 (Week 8) |
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