The effect of Fampridine-SR on cognitive fatigue in a randomized double-blind crossover trial in patients with MS.

BACKGROUND

Cognitive fatigue (CF) is a common complaint in persons with MS (PwMS). Fampridine-SR improves ambulation, fatigue and endurance, due to enhancing action potential formation by blocking potassium channels in demyelinated axons. Thus, through this same mechanism, it is hypothesized that Fampridine-SR could improve CF.

OBJECTIVE

To determine if Fampridine-SR objectively improves CF in PwMS.

METHODS

Sixty PwMS of any type with CF, defined as 3 or less correct responses when comparing the last third to the first third on the Paced Auditory Serial Addition Test (PASAT), were recruited from a tertiary care MS clinic in London (ON) Canada. Subjects also had to be between 18 and 64 years of age, inclusive, not had a relapse in the last 60 days or corticosteroids in the last 30 days, EDSS 0.0-7.0, and no other diagnosis that could cause cognitive impairment. A randomized double blind crossover design was used: subjects were randomized to either placebo or Fampridine-SR for 4 weeks, then after at least a one week washout, received the opposite treatment. Subjects were assessed before and after each treatment block. The primary outcome was the PASAT CF score after treatment with Fampridine-SR compared to placebo. T-tests and chi-square were used to compare demographics between the two groups (placebo-Fampridine-SR vs. Fampridine SR-placebo). Treatment effects were assessed using factorial ANOVA, with treatment (Fampridine-SR vs. placebo) and time (before and after treatment) as within-subject variables.

RESULTS

Of the 60 subjects randomized, 48 completed the study; three were removed due to an adverse event while in the treatment arm (one due to relapse while on placebo, one due to urinary retention and one due to dizziness and headache while on Fampridine-SR). The subjects had a mean age of 46.5±10.0 years, education of 13.6±1.9 years, and were diagnosed with MS 10.6±9.6 years ago. The majority were female (46, 76.7%), had relapsing remitting MS (41, 68.3%) with median EDSS of 3.5 (range 1.0-7.0). There were no significant demographic differences between the two groups. The treatment x time interaction within the factorial ANOVA on PASAT CF scores was statistically significant, F(1, 45)=8.28, p=0.006, suggesting there is a difference between the treatments (placebo vs. Fampridine-SR), over the course of the study. An evaluation of the mean scores suggests, however, that subjects saw a greater improvement when they were given the placebo, than when they were given the active medication. Similarly, individuals showed a greater increase in their information processing speed (as measured by the PASAT) over the course of treatment when they were given the placebo, as compared with the active medication F(1,45)=4.17, p=0.047.

CONCLUSIONS

Although this small pilot study does not suggest that Fampridine-SR results in a statistically significant improvement of CF in MS patients, as compared to placebo, individuals demonstrated an improvement in both information processing speed and CF, suggesting further studies are warranted.