Clinical trial NCT02849782: Short and Long Term Multiple Outcomes in Persons With Multiple Sclerosis Treated by Fampridine.
Official title: Short and Long Term Fampridine Treatment in Persons With Multiple Sclerosis: Cognitive and Motor Performances
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Gait analysis
Fampridine
Fatigue
Daily activity
Cognition
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2016-07-29
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: 6 Minute Walk Test (6MWT)
timeFrame: Timed 21 days
Secondary outcomes:
measure: Verbal fluencies
timeFrame: Day 1
measure: Verbal fluencies
timeFrame: 7 days
measure: Verbal fluencies
timeFrame: 21 days
measure: Verbal fluencies
timeFrame: 28 days
measure: Verbal fluencies
timeFrame: up to one year
measure: Symbol Digit Modalities Test
timeFrame: Day 1
measure: Symbol Digit Modalities Test
timeFrame: 7 days
measure: Symbol Digit Modalities Test
timeFrame: 21 days
measure: Symbol Digit Modalities Test
timeFrame: 28 days
measure: Symbol Digit Modalities Test
timeFrame: up to one year
measure: Modified Fatigue Impact Scale (mFIS)
timeFrame: day 1
measure: Modified Fatigue Impact Scale (mFIS)
timeFrame: 7 days
measure: Modified Fatigue Impact Scale (mFIS)
timeFrame: 21 days
measure: Modified Fatigue Impact Scale (mFIS)
timeFrame: 28 days
measure: Modified Fatigue Impact Scale (mFIS)
timeFrame: up to one year
measure: Fatigue Severity Scale (FSS)
timeFrame: day 1
measure: Fatigue Severity Scale (FSS)
timeFrame: 7 days
measure: Fatigue Severity Scale (FSS)
timeFrame: 21 days
measure: Fatigue Severity Scale (FSS)
timeFrame: 28 days
measure: Fatigue Severity Scale (FSS)
timeFrame: up to one year
measure: Multiple Sclerosis Walking Scale 12 (MSWS12)
timeFrame: day 1
measure: Multiple Sclerosis Walking Scale 12 (MSWS12)
timeFrame: 7 days
measure: Multiple Sclerosis Walking Scale 12 (MSWS12)
timeFrame: 21 days
measure: Multiple Sclerosis Walking Scale 12 (MSWS12)
timeFrame: 28 days
measure: Multiple Sclerosis Walking Scale 12 (MSWS12)
timeFrame: up to one year
measure: "PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)
timeFrame: day 1
measure: "PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)
timeFrame: day 7
measure: "PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)
timeFrame: day 21
measure: "PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)
timeFrame: day 28
measure: "PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)
timeFrame: up to one year
measure: Physical activity in real life condition
timeFrame: During 7 days (day 1 to day 7)
measure: Physical activity in real life condition
timeFrame: During 7 days (day 21 to day 28)
measure: Timed 25 Walk Test (T25WT)
timeFrame: Day 1
measure: Timed 25 Walk Test (T25WT)
timeFrame: 7 days
measure: Timed 25 Walk Test (T25WT)
timeFrame: 21 days
measure: Timed 25 Walk Test (T25WT)
timeFrame: 28 days
measure: Timed 25 Walk Test (T25WT)
timeFrame: up to one year
measure: Timed Up and Go test (TUG)
timeFrame: Day 1
measure: Timed Up and Go test (TUG)
timeFrame: 7 days
measure: Timed Up and Go test (TUG)
timeFrame: 21
measure: Timed Up and Go test (TUG)
timeFrame: 28 days
measure: Timed Up and Go test (TUG)
timeFrame: up to one year
measure: 6 Minute Walk Test (6MWT)
timeFrame: day 1
measure: 6 Minute Walk Test (6MWT)
timeFrame: day 7
measure: 6 Minute Walk Test (6MWT)
timeFrame: day 28
measure: 6 Minute Walk Test (6MWT)
timeFrame: up to one year
Other outcomes:
Locations:
city: Besancon
country: France
facility: CHU Jean Minjoz
Study officials:
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