Muscle Spasticity, Spinal Cord Injury
Conditions
Keywords
spinal cord injury, muscle spasticity
Brief summary
Normally, nerve fibers carry electrical impulses through the spinal cord, providing communication between the brain and the arms and legs. In people with spinal cord injury, some fibers may be destroyed at the site of injury, while others remain connected but do not work correctly to carry electrical impulses. As a result, subjects with an incomplete spinal cord injury may have spasticity which is muscle spasms or muscle stiffness that makes movement difficult. Fampridine-SR is an experimental drug that increases the ability of the nerve to conduct electrical impulses. This study will examine the effects of Fampridine-SR on moderate to severe lower-limb spasticity, as well as the effects on bodily functions such as bladder control, bowel function and sexual function. The study will also examine the possible risks of taking Fampridine-SR.
Interventions
DRUGFampridine-SR
25mg bid (twice daily)
OTHERPlacebo
Placebo
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Incomplete traumatic Spinal Cord Injury (at least 18 months prior and stable for 6 months) * Moderate to severe lower-limb spasticity * Able to give informed consent and willing to comply with protocol
Exclusion criteria
* Pregnancy * History of seizures * Existing or history of frequent Urinary Tract Infections * History of drug or alcohol abuse * Allergy to pyridine-containing substances * Received a botox injection 4 months prior to study * Received an investigational drug within 30 days * Previously treated with 4-aminopyridine (4-AP) * Not on stable medication dosing in 3 weeks prior to study * Abnormal ECG or laboratory value at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity | Baseline (visits 2,3) average score days 7,14 and double blind treatment period (visits 4-7) average score days 28-98 | The Ashworth Score is the average rating (based on a scale of 1 to 5) of four lower extremity muscle groups; left and right knee flexors and extensors (hamstrings and quadriceps muscles). A higher Ashworth Score indicates a greater degree of abnormal muscle tone (spasticity) and a negative change in score indicates improvement. |
| Double-blind Change From Baseline in Subject's Global Impression (SGI) of Treatment | Baseline (visits 2,3) average score days 7,14 and double blind treatment period (visits 4-7) average score days 28-98 | This questionnaire asked the patient to evaluate the effects of investigational drug on his/her quality of life during the preceding week using a 7-point scale (from 1=terrible to 7=delighted). A positive change score in SGI indicates improved outcome. |
Countries
Canada, United States
Participant flow
Recruitment details
The target population consists of patients with chronic incomplete spinal cord injury (SCI) whose injury occurred at least 18 months prior to screening, and whose neurological status has been stable for at least 6 months.
Pre-assignment details
One patient did not take any investigational drug and was excluded from the safety and ITT populations. The remaining 212 patients were included in the ITT and safety populations: 98 in the placebo and 114 in the Fampridine-SR 25 mg b.i.d. group.
Participants by arm
| Arm | Count |
|---|---|
| Fampridine-SR 50mg/Day Fampridine-SR : 25mg bid (twice daily) | 114 |
| Placebo Placebo : Placebo | 98 |
| Total | 212 |
Baseline characteristics
| Characteristic | Placebo | Total | Fampridine-SR 50mg/Day |
|---|---|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 13.1 | 40.9 years STANDARD_DEVIATION 12.54 | 41.6 years STANDARD_DEVIATION 12.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 30 Participants | 18 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 | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 81 Participants | 175 Participants | 94 Participants |
| Sex: Female, Male Female | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Male | 85 Participants | 185 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 114 | 84 / 98 |
| serious Total, serious adverse events | 6 / 114 | 6 / 98 |
Outcome results
Primary
Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity
The Ashworth Score is the average rating (based on a scale of 1 to 5) of four lower extremity muscle groups; left and right knee flexors and extensors (hamstrings and quadriceps muscles). A higher Ashworth Score indicates a greater degree of abnormal muscle tone (spasticity) and a negative change in score indicates improvement.
Time frame: Baseline (visits 2,3) average score days 7,14 and double blind treatment period (visits 4-7) average score days 28-98
Population: Intent to treat (ITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fampridine-SR 50mg/Day | Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity | -0.19 units on a scale | Standard Error 0.039 |
| Placebo | Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity | -0.15 units on a scale | Standard Error 0.042 |
Primary
Double-blind Change From Baseline in Subject's Global Impression (SGI) of Treatment
This questionnaire asked the patient to evaluate the effects of investigational drug on his/her quality of life during the preceding week using a 7-point scale (from 1=terrible to 7=delighted). A positive change score in SGI indicates improved outcome.
Time frame: Baseline (visits 2,3) average score days 7,14 and double blind treatment period (visits 4-7) average score days 28-98
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fampridine-SR 50mg/Day | Double-blind Change From Baseline in Subject's Global Impression (SGI) of Treatment | -0.2 units on a scale | Standard Error 0.08 |
| Placebo | Double-blind Change From Baseline in Subject's Global Impression (SGI) of Treatment | -0.1 units on a scale | Standard Error 0.09 |