NCT02391961

Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis

Completed Phase 2 Results posted Last updated 4 September 2020

What this trial tests

Phase 2 trial testing Dalfampridine in Multiple Sclerosis in 23 participants. Completed in 31 March 2019.

Timeline

1 April 2015

Primary endpoint
31 January 2019

31 March 2019

Quick facts

Lead sponsor	VA Office of Research and Development
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	basic science
Enrollment	23
Start date	1 April 2015
Primary completion	31 January 2019
Estimated completion	31 March 2019
Sites	1 location across United States

Drugs / interventions tested

• Dalfampridine — full drug profile →
• Placebo

Conditions studied

• Multiple Sclerosis — all drugs for Multiple Sclerosis →
• Internuclear Ophthalmoplegia — all drugs for Internuclear Ophthalmoplegia →
• Fatigue — all drugs for Fatigue →

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 18 to 65, any sex, with Multiple Sclerosis or Internuclear Ophthalmoplegia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pulse Size Ratio (PSR): Abducting/Adducting Eye Ratio for Saccadic Peak Velocity. Primary · Average PSR values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

For each saccade made by the subject, the ratio of the maximum velocity (deg/sec) of the eye moving away from the nose and of the eye moving towards the nose was calculated. Subjects' horizontal saccades were recorded for 10 minutes, and an average of PSR for all saccades recorded was taken.

average pulse size ratio baseline

Group	Value	95% CI
Dalfampridine	1.914	± 0.454
Placebo	1.937	± 0.553

average pulse size ratio after 3 hours

Group	Value	95% CI
Dalfampridine	1.805	± 0.451
Placebo	1.898	± 0.508

Pulse Time Delay (PTD): Time Difference Between Onset of the Saccade in the Adducting Eye and Onset of the Saccade in the Abducting Eye. Primary · Average PTD values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

For each saccade made by the subject, we calculated the difference (in sec) between the onset (based on a velocity threshold) of the movement in the adducting eye (the eye moving towards the nose) and the onset of the movement in the abducting eye (the eye moving away from the nose). Subjects' horizontal saccades were recorded for 10 minutes, and an average of PTD for all saccades recorded was taken.

Average PTD at baseline

Group	Value	95% CI
Dalfampridine	0.007	± 0.005
Placebo	0.007	± 0.005

Average PTD after 3 hours

Group	Value	95% CI
Dalfampridine	0.008	± 0.004
Placebo	0.008	± 0.004

Reading Acuity (RA) Secondary · Average RA values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

MNREAD acuity charts for reading acuity (RA)

RA at baseline

Group	Value	95% CI
Dalfampridine	0.111	± 0.117
Placebo	0.108	± 0.138

RA after 3 hours

Group	Value	95% CI
Dalfampridine	0.088	± 0.121
Placebo	0.086	± 0.141

Maximum Reading Speed (MRS) Secondary · Average MRS values were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

MNREAD acuity charts for reading speed (maximum reading speed, MRS)

MRS at baseline

Group	Value	95% CI
Dalfampridine	156	± 31
Placebo	151.7	± 20

MRS after 3 hours

Group	Value	95% CI
Dalfampridine	158	± 19
Placebo	158.7	± 25

Gait Assessment Secondary · Measures were taken on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks), on each visit before (baseline) and three hours after taking the study pill.

25-foot Walk Test (FWT)

25 FWT baseline

Group	Value	95% CI
Dalfampridine	8.986	± 4.957
Placebo	9.113	± 4.639

25 FWT after 3 hours

Group	Value	95% CI
Dalfampridine	8.567	± 5.352
Placebo	9.184	± 5.400

National Eye Institute (NEI) Visual Function Questionnaire 25 (VFQ-25) Secondary · VFQ25 was administered on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks).

We used a validated questionnaire to assess visual disability, the National Eye Institute (NEI) Visual Function Questionnaire 25. Min value 0; Max value 100; Higher scores mean a better outcome.

Group	Value	95% CI
Dalfampridine	73.48	± 16.65
Placebo	71.62	± 22.3

10-Item Neuro-Ophthalmic Supplement (NOS) Secondary · 10-Item NOS was administered on day of visit 2 (after 4 weeks) and on day of visit 4 (after 10 weeks).

We used a validated questionnaire to assess visual disability, the 10-Item Neuro-Ophthalmic Supplement. Min value 0; Max value 100; Higher scores mean a better outcome.

Group	Value	95% CI
Dalfampridine	64.9	± 24
Placebo	64.3	± 25

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data was collected for each subject during their participation time in the study from time of enrollment to study completion or withdrawal, an average of 10 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dalfampridine

Serious: 0/17 (0%)

Deaths: 0/17

Placebo

Serious: 0/15 (0%)

Deaths: 0/15

Other adverse events (2 terms — click to expand)

Reaction	System	Dalfampridine	Placebo
known mild side effect of medication	Gastrointestinal disorders	—	—
known side effect of medication	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT02391961 adverse events section.

Sponsor's own description

Primary fatigue represents a major cause of disability in patients with multiple sclerosis (MS), being reported in about 90% of cases. Fatigue interferes with everyday functioning but, unfortunately, little is known about its mechanisms. The investigators propose a characteristic eye movement abnormality (internuclear ophthalmoparesis, INO), commonly encountered in MS, as a simple model for primary motor fatigue. The investigators described worsening of ocular performance in MS patients with INO following visual tasks (ocular motor fatigue), which is likely due to decreased neural conduction along brain pathways injured by MS. This mechanism could represent a major component of MS-related primary motor fatigue. Relevant to Veterans' care, INO is a significant cause of visual disability, especially when complicated by ocular fatigue, and limits daily activities such as reading and driving. The investigators propose a medical treatment to improve ocular performance/fatigue in INO, which can reduce visual disability and improve quality of life in Veterans with MS.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment.
   Serra A, Chisari CG, Matta M. · · 2018 · cited 51× · PMID 29467711 · DOI 10.3389/fneur.2018.00031