Short and Long Term Multiple Outcomes in Persons With Multiple Sclerosis Treated by Fampridine. (FAMPISEP)

Centre Hospitalier Universitaire de Besancon

Status and phase: Completed; Phase 4

Conditions: Multiple Sclerosis

Treatments: Drug: Fampridine

Study type: Interventional

Funder types: Other

Identifiers

NCT02849782

API/2014/49

Details and patient eligibility

About

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.

Full 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.

Enrollment: 89 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• MS diagnostic regarding the modified McDonald criteria
• EDSS status between 4.0 and 6.5
• patients able to walk during 6 minutes

Exclusion criteria

• increasing MS symptoms during the previous 60 days
• history of epilepsy or epileptic seizure
• immunotherapy change in the previous 60 days
• beginning anti-spastic treatment in the previous 30 days
• beginning treatment that is able to decrease fatigue symptoms in the previous 30 days
• modification of the rehabilitation program during the study
• renal insufficiency (creatinine clearance <80ml.min-1 given by the Cockroft-Gault formula)
• concomitant treatment by organic cation transporter 2 inhibitor
• hypersensitivity to fampridine

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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89 participants in 2 patient groups

Fampridine responder

Experimental group

Description:

Persons who have been diagnosed as Multiple Sclerosis according to Mc Donald Criteria : person with Multiple Sclerosis (PwMS). Fampridine was prescribed according to the guidelines issued by the French National Security Agency of Medicines and Health Products (ANSM) at the dose of 10 mg twice a day. According to official ANSM guidelines, the prescription is initially limited to 2 weeks of therapy, at which point a new assessment is performed by the medical practitioner to evaluate the clinical benefits. Fampridine responder is a PwMS with an improvement in the judgment of the practitioner.

Treatment:

Drug: Fampridine

Fampridine non responder

Active Comparator group

Description:

Persons who have been diagnosed as Multiple Sclerosis according to Mc Donald Criteria : person with Multiple Sclerosis (PwMS). Fampridine was prescribed according to the guidelines issued by the French National Security Agency of Medicines and Health Products (ANSM) at the dose of 10 mg twice a day. According to official ANSM guidelines, the prescription is initially limited to 2 weeks of therapy, at which point a new assessment is performed by the medical practitioner to evaluate the clinical benefits. Fampridine non responder is a PwMS without any improvement in the judgment of the practitioner.

Treatment:

Drug: Fampridine