Safety and Efficacy of Oral Fampridine-Sustained Release (SR) for the Treatment of Spasticity Resulting From Spinal Cord Injury
- Conditions
- Spinal Cord InjuryMuscle Spasticity
- Interventions
- Drug: Fampridine-SRDrug: Placebo
- Registration Number
- NCT01683838
- Lead Sponsor
- Acorda Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 204
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description fampridine-SR 50mg/day Fampridine-SR - Placebo Placebo -
- Primary Outcome Measures
Name Time Method 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 evaluates the functioning of two lower extremity muscle groups, the hamstring and quadriceps muscles, while in the supine position. The test measures extension of the right and left hamstring muscle and flexion of the right and left quadriceps muscle using the following 5-point grading scale:
1=no increased tone; 2=slight increase in tone, giving a "catch" when the affected part is moved in flexion or extension; 3=more marked increase in tone, but affected part is easily flexed; 4=considerable increase in tone, passive movement is difficult; 5=affected part is rigid in flexion and extension.
The Ashworth Score was determined by adding all individual scores for each muscle group and dividing by four. Higher Ashworth Scores indicated greater spasticity.Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98 The SGI is a 7-unit ordinal scale used by the subject to evaluate the effects of study medication on his/her quality of life during the preceding week, with higher scores denoting greater satisfaction. A positive change score in SGI signifies improved outcome.
The questionnaire consisted of one question (How do you feel about the effects of the investigational drug over the past 7 days?). The answer was based on a numerical rating scale where 1=terrible; 2=unhappy; 3=mostly dissatisfied; 4=neutral/mixed; 5=mostly satisfied; 6=pleased; 7=delighted.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Mean International Index of Erectile Function (IIEF) Score Baseline (visit 1) average score obtained at day 1 and stable treatment period (visit 7) average score day 98 Male patients were asked to complete the IIEF questionnaire on sexual function. The IIEF is a brief, reliable, and valid self-administered questionnaire of 15 questions (items) that were categorized into five domains: Erectile Function (EF) scores: 0-6 Severe dysfunction, 7-12 Moderate dysfunction, 13-18 Mild to moderate dysfunction, 19-24 Mild dysfunction, 25-30 No dysfunction. Orgasmic Function (OF) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Sexual Desire (SD) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Intercourse Satisfaction (IS) score range: 0-3 Severe dysfunction to 13-15 No dysfunction, and Overall Satisfaction (OS) score range: 0-2 Severe dysfunction to 9-10 No dysfunction.
Domain scores were derived by summing the individual items within a given domain. Final scale ranges from 0 (negative) to 5 (positive). A positive change in IIEF domain scores signifies improvement.Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98 Bowel/bladder questions pertaining to the average number of times per day the patient experienced accidental urination/leakage and the average number of bowel movements per day were asked of all patients daily.
A negative change in patient bladder/bowel function diary score signifies improvement.Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores Baseline (visits 2,3) average of days 7-14 and double-blind treatment period (visits 4-7) average of days 28-98) The supervising clinician rated the patient's neurological condition following treatment as compared to the screening visit on a seven-point scale (from 1=very much improved to 7=very much worse). The assessment was based on the clinician's overall impression of the patient's neurological status (specifically bowel, bladder, and sexual function; spasticity; and other neurological functions) and general state of health related to his or her participation in the study. Negative change scores indicated a change for the better.
Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score Baseline (visits 2,3) average score days 7,14 and stable-dose treatment period (visits 5-7) average score days 56-98 Ten key muscle groups for the right and left sides were rated on a 0 (absent) to 5 (normal) scale, with a possible total score of 100. Higher positive change scores indicate improved motor function.
Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores Baseline (visit 1) average score obtained at day 1 and stable treatment period (visits 4-7) average score days 28-98 The FSFI is a brief, reliable, and valid self-administered questionnaire of 19 questions (items). It contains six domains: Desire (2 items score range: 1 Very low or none at all to 5 Very high), Arousal (4 items score range: 0 No sexual activity to 5 Almost always or always), Lubrication (4 items score range: 0 No sexual activity to 5 Almost always or always), Orgasm (3 items score range: 0 No sexual activity to 5 Almost always or always), Satisfaction (3 items score range: 0 No sexual activity to 5 Very satisfied) and Pain (3 items score range: 0 Did not attempt intercourse to 5 Almost never or never).
A positive change signifies improvement.Adjusted Mean Change in Subject Bowel Function Diary Scores Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98 Bowel questions pertaining to the average number of minutes per day spent on bowel routine were asked of all patients daily.
A negative change in patient bowel function diary score signifies improvement.Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98 The Spasm Frequency score is the average rating by the clinician of the left and right arm(s) and leg(s), each evaluated on a 4-point scale (from 0=no spasms to 4=spontaneous spasms occurring more than ten times per hour), with higher scores denoting a greater degree of muscle spasms.
The Spasm Severity score is the average rating of the left and right arm(s) and leg(s), each evaluated on a three-point scale (mild, moderate, or severe) as rated by the clinician on the basis of patient self-report.
On both, a negative change in score signifies improvement in muscle spasms. The average Spasm Frequency/Spasm Severity Score was calculated as the average of the left and right non-missing scores.
Trial Locations
- Locations (30)
Craig Hospital
🇺🇸Englewood, Colorado, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
St. Mary's of the Lake Hospital
🇨🇦Kingston, Ontario, Canada
Rehabilitation Institute of Michigan
🇺🇸Detroit, Michigan, United States
Wood VA Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Minneapolis VA Hospital
🇺🇸Minneapolis, Minnesota, United States
UAB School of Medicine, 190 Spain Rehab Center
🇺🇸Birmingham, Alabama, United States
Long Beach VA Medical Center
🇺🇸Long Beach, California, United States
University of California, Davis
🇺🇸Sacramento, California, United States
Santa Clara Valley Medical Center
🇺🇸San Jose, California, United States
Hospital for Special Care
🇺🇸New Britain, Connecticut, United States
Hines VA Hospital
🇺🇸Hines, Illinois, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Missouri
🇺🇸Columbia, Missouri, United States
St. Louis University
🇺🇸Saint Louis, Missouri, United States
University of Rochester/Strong Memorial Hospital
🇺🇸Rochester, New York, United States
SUNY Upstate Clinical Trials Office
🇺🇸Syracuse, New York, United States
Helen Hayes Hospital
🇺🇸West Haverstraw, New York, United States
Charlotte Institute of Rehabilitation
🇺🇸Charlotte, North Carolina, United States
Coastal AHEC
🇺🇸Wilmington, North Carolina, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Miami Valley Hospital- Rehabilitation Institute of Medicine
🇺🇸Dayton, Ohio, United States
VA North Texas Health Care System
🇺🇸Dallas, Texas, United States
Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
INOVA Institute of Research and Education
🇺🇸Falls Church, Virginia, United States
Medical College of Virginia/VCU
🇺🇸Richmond, Virginia, United States
University of Washington Medical Center, Dept. of Rehabilitation
🇺🇸Seattle, Washington, United States
Health Sciences Centre
🇨🇦Winnipeg, Manitoba, Canada
Chedoke-McMaster Hospital
🇨🇦Hamilton, Ontario, Canada