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

Short and Long Term Fampridine Treatment in Persons With Multiple Sclerosis: Cognitive and Motor Performances

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Fampridine

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.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25030
    • CHU Jean Minjoz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fampridine responder; 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.	Drug: Fampridine; Oral intake of 10 mg twice daily; Other Names: Fampyra; code CIS : 62483787
Active Comparator: Fampridine non responder; 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.	Drug: Fampridine; Oral intake of 10 mg twice daily; Other Names: Fampyra; code CIS : 62483787

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute Walk Test (6MWT)	The 6MWT assessed the submaximal level of functional capacity. It was realized according to the recommendation of the American Thoracic Society. 6MWT instructions were read prior to each walk. Participants used his/her typical assistive device and walked around a circuit with 24-meters longer. If necessary, they were allowed to have a rest period and encouragement phrases were used each 30 seconds.	Timed 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal fluencies	Both semantic and phonological verbal fluencies were assessed in a quiet room. Semantic fluency was measured by asking patients to provide as many animal names as possible in 120 s. Different kinds of one sort of animal were accepted (e.g. kinds of birds or fish). Phonological fluency was measured by asking patients to provide as many words as possible beginning with the letter 'P' in 120 s. They were informed that proper nouns and words with the same stem would not be counted (e.g. pen, pencil). Patients were instructed to avoid repetitions.	Day 1
Verbal fluencies	Both semantic and phonological verbal fluencies were assessed in a quiet room. Semantic fluency was measured by asking patients to provide as many animal names as possible in 120 s. Different kinds of one sort of animal were accepted (e.g. kinds of birds or fish). Phonological fluency was measured by asking patients to provide as many words as possible beginning with the letter 'P' in 120 s. They were informed that proper nouns and words with the same stem would not be counted (e.g. pen, pencil). Patients were instructed to avoid repetitions.	7 days
Verbal fluencies	Both semantic and phonological verbal fluencies were assessed in a quiet room. Semantic fluency was measured by asking patients to provide as many animal names as possible in 120 s. Different kinds of one sort of animal were accepted (e.g. kinds of birds or fish). Phonological fluency was measured by asking patients to provide as many words as possible beginning with the letter 'P' in 120 s. They were informed that proper nouns and words with the same stem would not be counted (e.g. pen, pencil). Patients were instructed to avoid repetitions.	21 days
Verbal fluencies	Both semantic and phonological verbal fluencies were assessed in a quiet room. Semantic fluency was measured by asking patients to provide as many animal names as possible in 120 s. Different kinds of one sort of animal were accepted (e.g. kinds of birds or fish). Phonological fluency was measured by asking patients to provide as many words as possible beginning with the letter 'P' in 120 s. They were informed that proper nouns and words with the same stem would not be counted (e.g. pen, pencil). Patients were instructed to avoid repetitions.	28 days
Verbal fluencies	Both semantic and phonological verbal fluencies were assessed in a quiet room. Semantic fluency was measured by asking patients to provide as many animal names as possible in 120 s. Different kinds of one sort of animal were accepted (e.g. kinds of birds or fish). Phonological fluency was measured by asking patients to provide as many words as possible beginning with the letter 'P' in 120 s. They were informed that proper nouns and words with the same stem would not be counted (e.g. pen, pencil). Patients were instructed to avoid repetitions.	up to one year
Symbol Digit Modalities Test	The SDMT has a key at the top of the page with numbers and symbols; participants are required to refer to the key to correctly decode several lines of symbols. After completing sample items correctly, participants are timed for 90 s and the total number correct is their raw score. Only correct answers were account to the final score.	Day 1
Symbol Digit Modalities Test	The SDMT has a key at the top of the page with numbers and symbols; participants are required to refer to the key to correctly decode several lines of symbols. After completing sample items correctly, participants are timed for 90 s and the total number correct is their raw score. Only correct answers were account to the final score.	7 days
Symbol Digit Modalities Test	The SDMT has a key at the top of the page with numbers and symbols; participants are required to refer to the key to correctly decode several lines of symbols. After completing sample items correctly, participants are timed for 90 s and the total number correct is their raw score. Only correct answers were account to the final score.	21 days
Symbol Digit Modalities Test	The SDMT has a key at the top of the page with numbers and symbols; participants are required to refer to the key to correctly decode several lines of symbols. After completing sample items correctly, participants are timed for 90 s and the total number correct is their raw score. Only correct answers were account to the final score.	28 days
Symbol Digit Modalities Test	The SDMT has a key at the top of the page with numbers and symbols; participants are required to refer to the key to correctly decode several lines of symbols. After completing sample items correctly, participants are timed for 90 s and the total number correct is their raw score. Only correct answers were account to the final score.	up to one year
Modified Fatigue Impact Scale (mFIS)	The FIS is a 40-item Standardized questionnaire validated for MS. For our study, we used the validated French version of the FIS in MS, called "EMIF-SEP". The EMIF-SEP is composed of 40 items organized into four dimensions (cognitive, physical, social role and psychological dimensions) with each items rated on a four point scale (4=it's always true, 3=it's sometimes true, 2=it's sometimes false, 1=it's always false) and the total fatigue scores are standardized from 0 (meaning no fatigue) to 100 (meaning high degree of fatigue). The forty items are divided into the four dimensions: cognitive (10 items), physical (14 items), social role (13 items) and psychological (4 items). Each dimension score was also standardized as a percentage like total score.	day 1
Modified Fatigue Impact Scale (mFIS)	The FIS is a 40-item Standardized questionnaire validated for MS. For our study, we used the validated French version of the FIS in MS, called "EMIF-SEP". The EMIF-SEP is composed of 40 items organized into four dimensions (cognitive, physical, social role and psychological dimensions) with each items rated on a four point scale (4=it's always true, 3=it's sometimes true, 2=it's sometimes false, 1=it's always false) and the total fatigue scores are standardized from 0 (meaning no fatigue) to 100 (meaning high degree of fatigue). The forty items are divided into the four dimensions: cognitive (10 items), physical (14 items), social role (13 items) and psychological (4 items). Each dimension score was also standardized as a percentage like total score.	7 days
Modified Fatigue Impact Scale (mFIS)	The FIS is a 40-item Standardized questionnaire validated for MS. For our study, we used the validated French version of the FIS in MS, called "EMIF-SEP". The EMIF-SEP is composed of 40 items organized into four dimensions (cognitive, physical, social role and psychological dimensions) with each items rated on a four point scale (4=it's always true, 3=it's sometimes true, 2=it's sometimes false, 1=it's always false) and the total fatigue scores are standardized from 0 (meaning no fatigue) to 100 (meaning high degree of fatigue). The forty items are divided into the four dimensions: cognitive (10 items), physical (14 items), social role (13 items) and psychological (4 items). Each dimension score was also standardized as a percentage like total score.	21 days
Modified Fatigue Impact Scale (mFIS)	The FIS is a 40-item Standardized questionnaire validated for MS. For our study, we used the validated French version of the FIS in MS, called "EMIF-SEP". The EMIF-SEP is composed of 40 items organized into four dimensions (cognitive, physical, social role and psychological dimensions) with each items rated on a four point scale (4=it's always true, 3=it's sometimes true, 2=it's sometimes false, 1=it's always false) and the total fatigue scores are standardized from 0 (meaning no fatigue) to 100 (meaning high degree of fatigue). The forty items are divided into the four dimensions: cognitive (10 items), physical (14 items), social role (13 items) and psychological (4 items). Each dimension score was also standardized as a percentage like total score.	28 days
Modified Fatigue Impact Scale (mFIS)	The FIS is a 40-item Standardized questionnaire validated for MS. For our study, we used the validated French version of the FIS in MS, called "EMIF-SEP". The EMIF-SEP is composed of 40 items organized into four dimensions (cognitive, physical, social role and psychological dimensions) with each items rated on a four point scale (4=it's always true, 3=it's sometimes true, 2=it's sometimes false, 1=it's always false) and the total fatigue scores are standardized from 0 (meaning no fatigue) to 100 (meaning high degree of fatigue). The forty items are divided into the four dimensions: cognitive (10 items), physical (14 items), social role (13 items) and psychological (4 items). Each dimension score was also standardized as a percentage like total score.	up to one year
Fatigue Severity Scale (FSS)	The FSS is a method of evaluating fatigue in PwMS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus. The FSS is designed to differentiate fatigue from clinical depression because both share some of the same symptoms. The FSS questionnaire is composed of 9 statements related to patients' subjective perception of fatigue and its consequences on everyday activities. Patients are asked to rate their level of agreement (toward 7) or disagreement (toward 0) with the 9 statements.	day 1
Fatigue Severity Scale (FSS)	The FSS is a method of evaluating fatigue in PwMS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus. The FSS is designed to differentiate fatigue from clinical depression because both share some of the same symptoms. The FSS questionnaire is composed of 9 statements related to patients' subjective perception of fatigue and its consequences on everyday activities. Patients are asked to rate their level of agreement (toward 7) or disagreement (toward 0) with the 9 statements.	7 days
Fatigue Severity Scale (FSS)	The FSS is a method of evaluating fatigue in PwMS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus. The FSS is designed to differentiate fatigue from clinical depression because both share some of the same symptoms. The FSS questionnaire is composed of 9 statements related to patients' subjective perception of fatigue and its consequences on everyday activities. Patients are asked to rate their level of agreement (toward 7) or disagreement (toward 0) with the 9 statements.	21 days
Fatigue Severity Scale (FSS)	The FSS is a method of evaluating fatigue in PwMS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus. The FSS is designed to differentiate fatigue from clinical depression because both share some of the same symptoms. The FSS questionnaire is composed of 9 statements related to patients' subjective perception of fatigue and its consequences on everyday activities. Patients are asked to rate their level of agreement (toward 7) or disagreement (toward 0) with the 9 statements.	28 days
Fatigue Severity Scale (FSS)	The FSS is a method of evaluating fatigue in PwMS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus. The FSS is designed to differentiate fatigue from clinical depression because both share some of the same symptoms. The FSS questionnaire is composed of 9 statements related to patients' subjective perception of fatigue and its consequences on everyday activities. Patients are asked to rate their level of agreement (toward 7) or disagreement (toward 0) with the 9 statements.	up to one year
Multiple Sclerosis Walking Scale 12 (MSWS12)	The original scoring provides options 1-5 for each item, with 1 meaning no limitation and 5 meaning extreme limitation on the gait-related item.	day 1
Multiple Sclerosis Walking Scale 12 (MSWS12)	The original scoring provides options 1-5 for each item, with 1 meaning no limitation and 5 meaning extreme limitation on the gait-related item.	7 days
Multiple Sclerosis Walking Scale 12 (MSWS12)	The original scoring provides options 1-5 for each item, with 1 meaning no limitation and 5 meaning extreme limitation on the gait-related item.	21 days
Multiple Sclerosis Walking Scale 12 (MSWS12)	The original scoring provides options 1-5 for each item, with 1 meaning no limitation and 5 meaning extreme limitation on the gait-related item.	28 days
Multiple Sclerosis Walking Scale 12 (MSWS12)	The original scoring provides options 1-5 for each item, with 1 meaning no limitation and 5 meaning extreme limitation on the gait-related item.	up to one year
"PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)	The PERSEPP scale was used to evaluate the HRQoL of patients with MS (Baroin et al. 2013). This scale takes into account several aspects of HRQoL distributed across 66 items (described below) and includes relapse phases. Each item contains 6 response types according to a Likert scale where "0" was "strongly disagree" and "5" was "strongly agree". The PERSEPP scale has been validated in the French language	day 1
"PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)	The PERSEPP scale was used to evaluate the HRQoL of patients with MS (Baroin et al. 2013). This scale takes into account several aspects of HRQoL distributed across 66 items (described below) and includes relapse phases. Each item contains 6 response types according to a Likert scale where "0" was "strongly disagree" and "5" was "strongly agree". The PERSEPP scale has been validated in the French language	day 7
"PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)	The PERSEPP scale was used to evaluate the HRQoL of patients with MS (Baroin et al. 2013). This scale takes into account several aspects of HRQoL distributed across 66 items (described below) and includes relapse phases. Each item contains 6 response types according to a Likert scale where "0" was "strongly disagree" and "5" was "strongly agree". The PERSEPP scale has been validated in the French language	day 21
"PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)	The PERSEPP scale was used to evaluate the HRQoL of patients with MS (Baroin et al. 2013). This scale takes into account several aspects of HRQoL distributed across 66 items (described below) and includes relapse phases. Each item contains 6 response types according to a Likert scale where "0" was "strongly disagree" and "5" was "strongly agree". The PERSEPP scale has been validated in the French language	day 28
"PERception de la Sclérose En Plaques et de ses Poussées" (PERSEPP)	The PERSEPP scale was used to evaluate the HRQoL of patients with MS (Baroin et al. 2013). This scale takes into account several aspects of HRQoL distributed across 66 items (described below) and includes relapse phases. Each item contains 6 response types according to a Likert scale where "0" was "strongly disagree" and "5" was "strongly agree". The PERSEPP scale has been validated in the French language	up to one year
Physical activity in real life condition	The physical activity in real-life condition was measured with an ActiGraph, model wGT3X (Actigraph corp, USA), consistent with previous research on validating accelerometer output in PwMS. The accelerometer was sampled at 30 Hz and values were expressed as number of counts per minute. Participants were instructed to wear the accelerometer on an elastic belt around the waist (i.e. near to the center of displacement of body mass) located above the hip at the non-dominant side ; to wear it for a 7-day period (including a weekend); and to wear it for the whole day from getting out of bed in the morning until getting into bed in the evening. These instructions were summarized in a memo and given to participants.	During 7 days (day 1 to day 7)
Physical activity in real life condition	The physical activity in real-life condition was measured with an ActiGraph, model wGT3X (Actigraph corp, USA), consistent with previous research on validating accelerometer output in PwMS. The accelerometer was sampled at 30 Hz and values were expressed as number of counts per minute. Participants were instructed to wear the accelerometer on an elastic belt around the waist (i.e. near to the center of displacement of body mass) located above the hip at the non-dominant side ; to wear it for a 7-day period (including a weekend); and to wear it for the whole day from getting out of bed in the morning until getting into bed in the evening. These instructions were summarized in a memo and given to participants.	During 7 days (day 21 to day 28)
Timed 25 Walk Test (T25WT)	According with the recommendation of Cutter et al., participants were asked to walk on a 25 feet (7.62 m) distance. After appropriate instructions and familiarization, participants were asked to perform three gait tasks: walking at their self-selected comfortable speed .	Day 1
Timed 25 Walk Test (T25WT)	According with the recommendation of Cutter et al., participants were asked to walk on a 25 feet (7.62 m) distance. After appropriate instructions and familiarization, participants were asked to perform three gait tasks: walking at their self-selected comfortable speed .	7 days
Timed 25 Walk Test (T25WT)	According with the recommendation of Cutter et al., participants were asked to walk on a 25 feet (7.62 m) distance. After appropriate instructions and familiarization, participants were asked to perform three gait tasks: walking at their self-selected comfortable speed .	21 days
Timed 25 Walk Test (T25WT)	According with the recommendation of Cutter et al., participants were asked to walk on a 25 feet (7.62 m) distance. After appropriate instructions and familiarization, participants were asked to perform three gait tasks: walking at their self-selected comfortable speed .	28 days
Timed 25 Walk Test (T25WT)	According with the recommendation of Cutter et al., participants were asked to walk on a 25 feet (7.62 m) distance. After appropriate instructions and familiarization, participants were asked to perform three gait tasks: walking at their self-selected comfortable speed .	up to one year
Timed Up and Go test (TUG)	The TUG is a clinical test to assess the level of gait and balance. For its realization, a 47-cm-high chair with arm- and backrest was used. The 3-meters distance was marked with a tape on the floor and a cone marked the turning point. Participants were instructed to get up from the chair, walk 3 meters, turn around the cone and come back to sit on the chair. Participants were encouraged to walk as quickly as possible with safety consistency. After a familiarization trial, the TUG was performed twice. A third trial was applied if a difference of 10% was found between the two first trials. The mean value computed from the two closest trials was taken into account.	Day 1
Timed Up and Go test (TUG)	The TUG is a clinical test to assess the level of gait and balance. For its realization, a 47-cm-high chair with arm- and backrest was used. The 3-meters distance was marked with a tape on the floor and a cone marked the turning point. Participants were instructed to get up from the chair, walk 3 meters, turn around the cone and come back to sit on the chair. Participants were encouraged to walk as quickly as possible with safety consistency. After a familiarization trial, the TUG was performed twice. A third trial was applied if a difference of 10% was found between the two first trials. The mean value computed from the two closest trials was taken into account.	7 days
Timed Up and Go test (TUG)	The TUG is a clinical test to assess the level of gait and balance. For its realization, a 47-cm-high chair with arm- and backrest was used. The 3-meters distance was marked with a tape on the floor and a cone marked the turning point. Participants were instructed to get up from the chair, walk 3 meters, turn around the cone and come back to sit on the chair. Participants were encouraged to walk as quickly as possible with safety consistency. After a familiarization trial, the TUG was performed twice. A third trial was applied if a difference of 10% was found between the two first trials. The mean value computed from the two closest trials was taken into account.	21
Timed Up and Go test (TUG)	The TUG is a clinical test to assess the level of gait and balance. For its realization, a 47-cm-high chair with arm- and backrest was used. The 3-meters distance was marked with a tape on the floor and a cone marked the turning point. Participants were instructed to get up from the chair, walk 3 meters, turn around the cone and come back to sit on the chair. Participants were encouraged to walk as quickly as possible with safety consistency. After a familiarization trial, the TUG was performed twice. A third trial was applied if a difference of 10% was found between the two first trials. The mean value computed from the two closest trials was taken into account.	28 days
Timed Up and Go test (TUG)	The TUG is a clinical test to assess the level of gait and balance. For its realization, a 47-cm-high chair with arm- and backrest was used. The 3-meters distance was marked with a tape on the floor and a cone marked the turning point. Participants were instructed to get up from the chair, walk 3 meters, turn around the cone and come back to sit on the chair. Participants were encouraged to walk as quickly as possible with safety consistency. After a familiarization trial, the TUG was performed twice. A third trial was applied if a difference of 10% was found between the two first trials. The mean value computed from the two closest trials was taken into account.	up to one year
6 Minute Walk Test (6MWT)	The 6MWT assessed the submaximal level of functional capacity. It was realized according to the recommendation of the American Thoracic Society. 6MWT instructions were read prior to each walk. Participants used his/her typical assistive device and walked around a circuit with 24-meters longer. If necessary, they were allowed to have a rest period and encouragement phrases were used each 30 seconds.	day 1
6 Minute Walk Test (6MWT)	The 6MWT assessed the submaximal level of functional capacity. It was realized according to the recommendation of the American Thoracic Society. 6MWT instructions were read prior to each walk. Participants used his/her typical assistive device and walked around a circuit with 24-meters longer. If necessary, they were allowed to have a rest period and encouragement phrases were used each 30 seconds.	day 7
6 Minute Walk Test (6MWT)	The 6MWT assessed the submaximal level of functional capacity. It was realized according to the recommendation of the American Thoracic Society. 6MWT instructions were read prior to each walk. Participants used his/her typical assistive device and walked around a circuit with 24-meters longer. If necessary, they were allowed to have a rest period and encouragement phrases were used each 30 seconds.	day 28
6 Minute Walk Test (6MWT)	The 6MWT assessed the submaximal level of functional capacity. It was realized according to the recommendation of the American Thoracic Society. 6MWT instructions were read prior to each walk. Participants used his/her typical assistive device and walked around a circuit with 24-meters longer. If necessary, they were allowed to have a rest period and encouragement phrases were used each 30 seconds.	up to one year

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Publications and helpful links

General Publications

• Goodman AD, Brown TR, Edwards KR, Krupp LB, Schapiro RT, Cohen R, Marinucci LN, Blight AR; MSF204 Investigators. A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol. 2010 Oct;68(4):494-502. doi: 10.1002/ana.22240.
• Allart E, Benoit A, Blanchard-Dauphin A, Tiffreau V, Thevenon A, Zephir H, Outteryck O, Lacour A, Vermersch P. Sustained-released fampridine in multiple sclerosis: effects on gait parameters, arm function, fatigue, and quality of life. J Neurol. 2015 Aug;262(8):1936-45. doi: 10.1007/s00415-015-7797-1. Epub 2015 Jun 5.
• Almarwani M, Perera S, VanSwearingen JM, Sparto PJ, Brach JS. The test-retest reliability and minimal detectable change of spatial and temporal gait variability during usual over-ground walking for younger and older adults. Gait Posture. 2016 Feb;44:94-9. doi: 10.1016/j.gaitpost.2015.11.014. Epub 2015 Nov 30.
• Baert I, Freeman J, Smedal T, Dalgas U, Romberg A, Kalron A, Conyers H, Elorriaga I, Gebara B, Gumse J, Heric A, Jensen E, Jones K, Knuts K, Maertens de Noordhout B, Martic A, Normann B, Eijnde BO, Rasova K, Santoyo Medina C, Truyens V, Wens I, Feys P. Responsiveness and clinically meaningful improvement, according to disability level, of five walking measures after rehabilitation in multiple sclerosis: a European multicenter study. Neurorehabil Neural Repair. 2014 Sep;28(7):621-31. doi: 10.1177/1545968314521010. Epub 2014 Feb 6.
• Baroin A, Chopard G, Siliman G, Michoudet C, Vivot A, Vidal C, Mokadym H, Lavier A, Berger E, Rumbach L, Rude N. Validation of a new quality of life scale related to multiple sclerosis and relapses. Qual Life Res. 2013 Oct;22(8):1943-54. doi: 10.1007/s11136-012-0334-0. Epub 2012 Dec 18.
• Bland JM, Altman DG. Measurement error. BMJ. 1996 Jun 29;312(7047):1654. doi: 10.1136/bmj.312.7047.1654. No abstract available.
• Brochet B, Deloire MS, Bonnet M, Salort-Campana E, Ouallet JC, Petry KG, Dousset V. Should SDMT substitute for PASAT in MSFC? A 5-year longitudinal study. Mult Scler. 2008 Nov;14(9):1242-9. doi: 10.1177/1352458508094398. Epub 2008 Jul 24.
• Confavreux C, Vukusic S. The clinical epidemiology of multiple sclerosis. Neuroimaging Clin N Am. 2008 Nov;18(4):589-622, ix-x. doi: 10.1016/j.nic.2008.09.002.
• Debouverie M, Pittion-Vouyovitch S, Louis S, Guillemin F. Validity of a French version of the fatigue impact scale in multiple sclerosis. Mult Scler. 2007 Sep;13(8):1026-32. doi: 10.1177/1352458507077942.
• de Vet HC, Terwee CB, Knol DL, Bouter LM. When to use agreement versus reliability measures. J Clin Epidemiol. 2006 Oct;59(10):1033-9. doi: 10.1016/j.jclinepi.2005.10.015. Epub 2006 Aug 10.
• Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. doi: 10.1093/clinids/18.supplement_1.s79.
• Givon U, Zeilig G, Achiron A. Gait analysis in multiple sclerosis: characterization of temporal-spatial parameters using GAITRite functional ambulation system. Gait Posture. 2009 Jan;29(1):138-42. doi: 10.1016/j.gaitpost.2008.07.011. Epub 2008 Oct 31.
• Goldman MD, Marrie RA, Cohen JA. Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls. Mult Scler. 2008 Apr;14(3):383-90. doi: 10.1177/1352458507082607. Epub 2007 Oct 17.
• Goodkin DE. EDSS reliability. Neurology. 1991 Feb;41(2 ( Pt 1)):332. doi: 10.1212/wnl.41.2_part_1.332. No abstract available.
• Goodman AD, Bethoux F, Brown TR, Schapiro RT, Cohen R, Marinucci LN, Henney HR 3rd, Blight AR; MS-F203, MS-F204, and Extension Study Investigators. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials. Mult Scler. 2015 Sep;21(10):1322-31. doi: 10.1177/1352458514563591. Epub 2015 Jan 12.
• Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ. Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12). Neurology. 2003 Jan 14;60(1):31-6. doi: 10.1212/wnl.60.1.31.
• Hobart J, Blight AR, Goodman A, Lynn F, Putzki N. Timed 25-foot walk: direct evidence that improving 20% or greater is clinically meaningful in MS. Neurology. 2013 Apr 16;80(16):1509-17. doi: 10.1212/WNL.0b013e31828cf7f3. Epub 2013 Mar 27.
• Kalron A, Dvir Z, Achiron A. Walking while talking--difficulties incurred during the initial stages of multiple sclerosis disease process. Gait Posture. 2010 Jul;32(3):332-5. doi: 10.1016/j.gaitpost.2010.06.002. Epub 2010 Jul 1.
• Kalron A. Gait variability across the disability spectrum in people with multiple sclerosis. J Neurol Sci. 2016 Feb 15;361:1-6. doi: 10.1016/j.jns.2015.12.012. Epub 2015 Dec 10.
• Learmonth YC, Dlugonski D, Pilutti LA, Sandroff BM, Klaren R, Motl RW. Psychometric properties of the Fatigue Severity Scale and the Modified Fatigue Impact Scale. J Neurol Sci. 2013 Aug 15;331(1-2):102-7. doi: 10.1016/j.jns.2013.05.023. Epub 2013 Jun 20.
• Learmonth YC, Paul L, McFadyen AK, Mattison P, Miller L. Reliability and clinical significance of mobility and balance assessments in multiple sclerosis. Int J Rehabil Res. 2012 Mar;35(1):69-74. doi: 10.1097/MRR.0b013e328350b65f.
• Moon Y, Wajda DA, Motl RW, Sosnoff JJ. Stride-Time Variability and Fall Risk in Persons with Multiple Sclerosis. Mult Scler Int. 2015;2015:964790. doi: 10.1155/2015/964790. Epub 2015 Dec 30.
• Motl RW, Dlugonski D, Suh Y, Weikert M, Fernhall B, Goldman M. Accelerometry and its association with objective markers of walking limitations in ambulatory adults with multiple sclerosis. Arch Phys Med Rehabil. 2010 Dec;91(12):1942-7. doi: 10.1016/j.apmr.2010.08.011.
• Motl RW, Sosnoff JJ, Dlugonski D, Pilutti LA, Klaren R, Sandroff BM. Walking and cognition, but not symptoms, correlate with dual task cost of walking in multiple sclerosis. Gait Posture. 2014 Mar;39(3):870-4. doi: 10.1016/j.gaitpost.2013.11.023. Epub 2013 Dec 14.
• Pilutti LA, Dlugonski D, Sandroff BM, Suh Y, Pula JH, Sosnoff JJ, Motl RW. Gait and six-minute walk performance in persons with multiple sclerosis. J Neurol Sci. 2013 Nov 15;334(1-2):72-6. doi: 10.1016/j.jns.2013.07.2511. Epub 2013 Jul 30.
• Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. doi: 10.1002/ana.20703.
• Sandroff BM, Pilutti LA, Motl RW. Does the six-minute walk test measure walking performance or physical fitness in persons with multiple sclerosis? NeuroRehabilitation. 2015;37(1):149-55. doi: 10.3233/NRE-151247.
• van Uden CJ, Besser MP. Test-retest reliability of temporal and spatial gait characteristics measured with an instrumented walkway system (GAITRite). BMC Musculoskelet Disord. 2004 May 17;5:13. doi: 10.1186/1471-2474-5-13.
• Vlaar AM, Wade DT. Verbal fluency assessment of patients with multiple sclerosis: test-retest and inter-observer reliability. Clin Rehabil. 2003 Nov;17(7):756-64. doi: 10.1191/0269215503cr674oa.
• Wajda DA, Motl RW, Sosnoff JJ. Dual task cost of walking is related to fall risk in persons with multiple sclerosis. J Neurol Sci. 2013 Dec 15;335(1-2):160-3. doi: 10.1016/j.jns.2013.09.021. Epub 2013 Sep 20.
• Magnin E, Sagawa Y, Moulin T, Decavel P. What Are the Minimal Detectable Changes in SDMT and Verbal Fluency Tests for Assessing Changes in Cognitive Performance in Persons with Multiple Sclerosis and Non-Multiple Sclerosis Controls? Eur Neurol. 2020;83(3):263-270. doi: 10.1159/000508607. Epub 2020 Jul 7.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2014
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: July 22, 2016
• First Submitted That Met QC Criteria: July 26, 2016
• First Posted (Estimate): July 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Fatigue; Cognition; Gait analysis; Fampridine; Daily activity
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: API/2014/49

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No