Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, MS, walking, leg strength, demyelination
Brief summary
The purpose of the study is to show that individuals treated with Fampridine-SR tablets are significantly more likely to have consistent improvements in their walking than those treated with placebo tablets.
Detailed description
Multiple sclerosis (MS) is a disorder of the body's immune system that affects the central nervous system (CNS). Normally, nerve fibers carry electrical impulses through the spinal cord, providing communication between the brain and the arms and legs. In people with MS, the fatty sheath that surrounds and insulates the nerve fibers (called myelin) deteriorates, causing nerve impulses to be slowed or stopped. As a result, patients with MS may experience periods of muscle weakness and other symptoms such as numbness, loss of vision, loss of coordination, paralysis, spasticity, mental and physical fatigue and a decrease in the ability to think and/or remember. These periods of illness may come (exacerbations) and go (remissions). Fampridine-SR is an experimental drug that has been reported to possibly improve muscle strength and walking ability for some people with MS. This study will evaluate the effects and possible risks of taking Fampridine-SR in MS patients
Interventions
DRUGFampridine-SR
Tablets, 10 mg, twice daily, 9 weeks
DRUGPlacebo
placebo (sugar pill)
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patient with clinically defined multiple sclerosis * All patients must be able to complete two trials of a timed 25 foot walk
Exclusion criteria
* Female patients who are either pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responders Based Upon the Timed 25-Foot Walk [T25FW] | Days -21, -14, -7, 0, 14, 28, 42, 56, 63, 77 | A responder is a patient who showed faster walking speed for at least 3 visits out of a possible 4 during the double-blind period than the maximum value achieved in the 5 non-double-blind no-treatment visits (4 before the double-blind period and one after) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lower Extremity Manual Muscle Test [LEMMT] | Days -21, -14, -7, 0, 14, 28, 42, 56, 63, 77 | Evaluator rated strength in hip flexors, knee flexors, knee extensors, and ankle dorsiflexors on the following scale: best value = 5.0 (normal muscle strength), worst value = 0.0 (absence of any voluntary contraction). A positive shift in LEMMT score shows improvement in strength. Change in LEMMT scores for the secondary efficacy measure was found by averaging the LEMMT scores on days 14, 28, 42, and 56 (double-blind treatment period) and subtracting the baseline LEMMT score. |
Countries
Canada, United States
Participant flow
Recruitment details
Patients with Multiple Sclerosis, enrolled at medical and MS clinics in USA and Canada; enrollment started 22 May 2007; last patient completed on 27 Feb 2008
Pre-assignment details
Two weeks of single-blind placebo run-in to establish baseline walking speeds
Participants by arm
| Arm | Count |
|---|---|
| Fampridine-SR 10 mg b.i.d. Treatment Fampridine-SR 10 mg b.i.d. dosing for 9 weeks | 120 |
| Placebo Treatment Placebo b.i.d. dosing for 9 weeks | 119 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 3 | 4 |
| Double-blind Treatment Period | Protocol inclusion deviation | 1 | 0 |
| Double-blind Treatment Period | Protocol Violation | 2 | 1 |
| Double-blind Treatment Period | Withdrawal due to AE before study began | 1 | 0 |
Baseline characteristics
| Characteristic | Fampridine-SR 10 mg b.i.d. Treatment | Placebo Treatment | Total |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 9.55 | 51.7 years STANDARD_DEVIATION 9.83 | 51.7 years STANDARD_DEVIATION 9.67 |
| Sex: Female, Male Female | 88 Participants | 74 Participants | 162 Participants |
| Sex: Female, Male Male | 32 Participants | 45 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 103 / 120 | 79 / 119 |
| serious Total, serious adverse events | 5 / 120 | 3 / 119 |
Outcome results
Primary
Responders Based Upon the Timed 25-Foot Walk [T25FW]
A responder is a patient who showed faster walking speed for at least 3 visits out of a possible 4 during the double-blind period than the maximum value achieved in the 5 non-double-blind no-treatment visits (4 before the double-blind period and one after)
Time frame: Days -21, -14, -7, 0, 14, 28, 42, 56, 63, 77
Population: Modified Intention-to-Treat \[ITT\] population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fampridine-SR 10 mg b.i.d. Treatment | Responders Based Upon the Timed 25-Foot Walk [T25FW] | 51 participants |
| Placebo Treatment | Responders Based Upon the Timed 25-Foot Walk [T25FW] | 11 participants |
Secondary
Change in Lower Extremity Manual Muscle Test [LEMMT]
Evaluator rated strength in hip flexors, knee flexors, knee extensors, and ankle dorsiflexors on the following scale: best value = 5.0 (normal muscle strength), worst value = 0.0 (absence of any voluntary contraction). A positive shift in LEMMT score shows improvement in strength. Change in LEMMT scores for the secondary efficacy measure was found by averaging the LEMMT scores on days 14, 28, 42, and 56 (double-blind treatment period) and subtracting the baseline LEMMT score.
Time frame: Days -21, -14, -7, 0, 14, 28, 42, 56, 63, 77
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fampridine-SR 10 mg b.i.d. Treatment | Change in Lower Extremity Manual Muscle Test [LEMMT] | 0.09 units on a scale | Standard Deviation 0.219 |
| Placebo Treatment | Change in Lower Extremity Manual Muscle Test [LEMMT] | 0.04 units on a scale | Standard Deviation 0.253 |