Prolonged-Release Fampridine As Adjunct Therapy to Active Enabled Motor Training in Multiple Sclerosis Patients: A Pilot, Double-Blind, Placebo-Controlled Study

Background: The walking impairment is a prominent manifestation of MS. Up to 85% of MS patients identify it as their primary complaint. Prolonged-release Fampridine (PRF) has been shown in multiple sclerosis patients to improve walking capabilities as measured by the timed 25 feet walk test. The effect of PRF on the benefit of exercice in MS has never been studied.

Objectives:

To investigate if multiple sclerosis (MS) subjects treated with PRF 10mg BID will show a greater benefit from active enabled motor training as compared with subjects treated with placebo.

Methods:

Single center, phase 4, pilot, placebo-controlled, double-blind 18 weeks study. 30 MS patients of all types, who satisfied PRF‘s product monograph prescribing criteria, were recruited. Half of the patients were randomized to receive PRF 10mg BID and the other half received placebo BID. All patients participated in active enabled motor training consisting of 3 sessions of 1 hour per week for a period of 6 weeks.  All patients then continued taking their medication (PRF or placebo) during a subsequent observational period of 8 weeks. Patients were evaluated at times -4, 0, 6 and 14 weeks using the timed 8 meters walk (8MW), the 6 minute walk (6MW) and the timed sit to stand (STS).

Results:

Both groups were balanced at baseline. The PRF treated group achieved a higher mean percent improvement from baseline in all three tasks at both the 6 and 14 week time points. The difference reached statistical significance (mean difference of 14.29, p=0.046) for the 8MW at the 14 week time point. A higher incidence of responders (>20% improvement from baseline) was seen in the PRF treated group at 6 weeks on the 8MW (odds ratio [OR] of 2.31) and the 6MW (OR of 1.63), and at 14 weeks on the 8MW and the STS (OR of 2.0).

Conclusions:

PRF in MS patients appears to enhance the benefit of active enabled motor training and to better sustain it over the following 8 weeks. Further studies are warranted.