Fatigue, Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, postural balance, gait, fatigue
Brief summary
Dalfampridine is a new medication that was FDA approved in 2010 to improve walking speed in people with Multiple Sclerosis (MS). People with MS walk slowly in part because MS damages the myelin insulation around nerves which slows conduction of messages from the brain to the leg muscles. Dalfampridine works by improving conduction in nerves with damaged myelin. Recent research indicates that imbalance in MS is in large part caused by poor conduction by the nerves that transmit information about the position of the legs to the brain. It is therefore likely that, by improving nerve conduction, dalfampridine will also improve imbalance in people with MS. Dalfampridine will be administered in this study by the same route (oral), dosage (10mg), and frequency (every 12 hours) approved by the FDA to improve walking speed in people with MS. The proposed pilot study will examine the effects of dalfampridine on imbalance in 24 subjects with Multiple Sclerosis (MS) and imbalance. This small pilot study will help to show if dalfampridine improves imbalance in MS and will guide the design and implementation of a larger full scale study to definitively determine if dalfampridine improves balance and prevents falls in people with MS.
Interventions
DRUGDalfampridine
10mg, bid, pill taken by mouth for 12 weeks
DRUGPlacebo
placebo pill, bid for 12 weeks
Sponsors
Acorda Therapeutics
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
* Age 20- 59 years, * Able to walk at least 100m without an aide or with unilateral assistance * Prolonged APR latencies (≥ 1SD \> mean for healthy people in this age range) OR, * Reduced balance-related activity (ABC scores ≤ 85%), * Abnormal trunk range of motion (horizontal), trunk range of motion (frontal), turning duration, cadence, double support time, stride length or gait cycle time (outside 1SD of the average for healthy people in this age range)
Exclusion criteria
* Currently taking dalfampridine (any within the last 2 weeks), * Cause(s) of imbalance other than MS, * Impaired renal function (creatinine clearance ≤50mL/min), * Seizure disorder * Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Automatic Postural Response (APR )Latency | Baseline to 12 weeks | Automatic Postural Response (APR) latencies will be measured by Computerized Dynamic Posturography (CDP). The restoration of balance after an unexpected movement by Computerized Dynamic Posturography relies on automated postural responses in the upper and lower legs, trunk, shoulders, and neck muscles. APR latency is the reaction- time response to movements of the support surface on which the subject stands. These responses typically occur at onset latencies of \ 100 milliseconds. In response to a change, both feet-in-place and stepping strategies can be used to recover balance, with the incidence of stepping responses becoming larger as the change magnitude increases voluntary movements in human subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores | Baseline to 12 weeks | The ABC is an 11-point scale and subjects are asked to indicate personal level of confidence in doing specific activities without losing balance or becoming unsteady on a scale from 0% to 100%. The ratings are added (possible range =0 -1600) and divide by 16 to get each subject's ABC score. A high ABC score indicates a high degree of confidence and a low ABC score indicates a low degree of confidence. |
| Change in Timed 25 Foot Walking Speed | Baseline to 12 weeks | — |
Countries
United States
Participant flow
Recruitment details
People with MS were recruited from several MS clinics in the Portland, OR metro area from September 2011 to August 2013. 24 subjects signed the consent and were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Dalfampridine Dalfampridine: 10mg, twice daily (bid), pill taken by mouth for 12 weeks | 12 |
| Placebo Placebo: placebo pill, twice daily (bid), for 12 weeks | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
Baseline characteristics
| Characteristic | Dalfampridine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 8.9 | 47.8 years STANDARD_DEVIATION 10.9 | 47.5 years STANDARD_DEVIATION 9.7 |
| MS Subtype Primary Progressive MS (PPMS) | 0 participants | 2 participants | 2 participants |
| MS Subtype Relapsing Remitting MS (RRMS) | 12 participants | 8 participants | 20 participants |
| MS Subtype Secondary Progressive MS (SPMS) | 0 participants | 2 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 12 | 10 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change in Automatic Postural Response (APR )Latency
Automatic Postural Response (APR) latencies will be measured by Computerized Dynamic Posturography (CDP). The restoration of balance after an unexpected movement by Computerized Dynamic Posturography relies on automated postural responses in the upper and lower legs, trunk, shoulders, and neck muscles. APR latency is the reaction- time response to movements of the support surface on which the subject stands. These responses typically occur at onset latencies of \ 100 milliseconds. In response to a change, both feet-in-place and stepping strategies can be used to recover balance, with the incidence of stepping responses becoming larger as the change magnitude increases voluntary movements in human subjects.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine | Change in Automatic Postural Response (APR )Latency | 5.71 milliseconds | Standard Deviation 16.2 |
| Placebo | Change in Automatic Postural Response (APR )Latency | 4.58 milliseconds | Standard Deviation 23 |
Comparison: t test comparing change in outcome between active and placebop-value: 0.51t-test, 2 sided
Secondary
Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores
The ABC is an 11-point scale and subjects are asked to indicate personal level of confidence in doing specific activities without losing balance or becoming unsteady on a scale from 0% to 100%. The ratings are added (possible range =0 -1600) and divide by 16 to get each subject's ABC score. A high ABC score indicates a high degree of confidence and a low ABC score indicates a low degree of confidence.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine | Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores | 1.30 Scores on a scale | Standard Deviation 9.02 |
| Placebo | Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores | 0.41 Scores on a scale | Standard Deviation 10.7 |
Comparison: t test comparing change in outcome between active and placebo after 12 weeks.p-value: 0.7t-test, 2 sided
Secondary
Change in Timed 25 Foot Walking Speed
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine | Change in Timed 25 Foot Walking Speed | 0.26 seconds | Standard Deviation 0.78 |
| Placebo | Change in Timed 25 Foot Walking Speed | 0.39 seconds | Standard Deviation 1.45 |
Comparison: t test comparing change in outcome between active and placebop-value: 0.8t-test, 2 sided