Short and Long Term Multiple Outcomes in Persons With Multiple Sclerosis Treated by Fampridine.
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 4

Summary: 
      This prospective monocentric open label trial was realized in the Laboratory of Clinical
      Functional Exploration of Movement at the University Hospital of Besancon. Cognitive
      evaluations: 7 days before fampridine treatment initiation (Pre 1), on the day of fampridine
      treatment initiation (Pre 2), 14 and 21 days after fampridine treatment initiation,
      respectively Post 1 and Post 2. Gait evaluations were assessed at Pre 1, Pre 2 and Post 1.

      Fampridine was prescribed according to guidelines issued by the French Health Products Safety
      Agency at the dose of 10 mg twice daily. Fampridine is indicated for the improvement of
      walking in MS patients with a walking disability (EDSS 4-6.5). A walking test is recommended
      to evaluate improvement after 2 weeks of treatment. According to the practitioner evaluation
      between Pre 2 and Post 1 (i.e. before and after fampridine treatment), patients were
      classified into 2 groups: responders whose clinical status was improved and non-responders
      whose clinical status was not improved.
    

Detailed description: 
      Multiple sclerosis (MS) is a chronic neurological disorder affecting young and middle-aged
      adults with a female to male ratio of more than 3:1. The cause of MS is unknown although it
      involves genetic susceptibility and environmental exposure. Since there is no known cure for
      MS, the main goals of treatment is to delay progression of the disease and to improve
      health-related quality of life (HRQoL) by masking patients' symptoms. Among several symptoms
      of MS (e.g., motor and cognitive impairments, optic neuritis, fatigue, pain, urinary
      dysfunction), gait impairment, defined as an activity limitation by the International
      Classification of Functioning Disability and Health, is one of the most common and disabling
      dysfunction in Persons with Multiple Sclerosis PwMS. Studies have reported that approximately
      75 % of individuals with MS experience clinically significant walking disturbances. Likewise,
      fatigue, impairment of information-processing speed (IPS), attention, working memory and
      executive functions can occur in MS and can worsen during the evolution of the disease.

      Studies have shown that MS symptomatic treatment by fampridine (4-aminopyridine) is
      associated with improvements in walking and muscle strength and possibly with cognition,
      vision, fatigue and spasticity. Indeed, fampridine is a potassium channel blocker which
      reduces the leakage of ionic current through these channels, prolonging repolarization and
      thus, enhancing action-potential formation in demyelinated axons. Presumably, by enhancing
      action-potential formation, more impulses might be conducted in the central nervous system
      (CNS) and neurological functions could be ameliorated. In recent phase III studies, Goodman
      et al. investigated the fampridine effect on the walk of individuals with MS during a timed
      25-foot walk test (T25FW). Improvement in walking velocity (≈25 % from baseline) was found
      for 35-43 % of the individuals in the interventional group.

      However, improvement in neuronal conduction induced by fampridine might not be limited to
      short distances of gait or even to motor functions and might also improve long distance
      ambulation or cognitive functions.

      Different assessments have been used for measuring gait impairments in multiple sclerosis,
      including the Timed 25-Foot Walk (T25FW), Six-Minute Walk Test (6MWT), spatio-temporal gait
      parameters measured with an instrumented walkway or the Timed Up and Go test (TUG). These
      different assessments can be performed at different conditions: simple task, fast speed or
      dual task. In this last case, the gait is associated with a cognitive or another motor task.
      For cognitive assessments, Symbol Digit Modalities Test (SDMT) and verbal fluencies have been
      used in previous studies.

      The aimed of the study was to evaluate the impact of fampridine in gait evaluating by long
      distance tests and to evaluate the impact of fampridine in fatigue and cognition.

      Assessments of patients were performed 7 days before fampridine treatment initiation (Pre 1),
      on the day of fampridine treatment initiation (Pre 2), 14 and 21 days after fampridine
      treatment initiation, respectively Post 1 and Post 2. Gait evaluations were assessed at Pre
      1, Pre 2 and Post 1. The first two assessments were intended to evaluate the variability of
      measurement without any treatment. A measurement of activity was performed by accelerometer
      during the period covering the first two assessments. The third assessment was intend to
      measure clinical improvements. The fourth seeks to show a potentially delayed action of
      fampridine on cognition.
    

Intervention name(s): Fampridine
Intervention type(s): Drug
Intervention description(s): Oral intake of 10 mg twice daily
Other intervention name(s): Fampyra; code CIS : 62483787
Intervention MeSH terms: 4-Aminopyridine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Gait analysis; Fampridine; Fatigue; Daily activity; Cognition