Clinical trial NCT01621113: Combination Therapy With Dalfampridine and Locomotor Training for Chronic, Motor Incomplete Spinal Cord Injury
Official title: Restoring Lost Functions After Spinal Cord Injury: Combination Therapy With Dalfampridine and Locomotor Training for Persons With Chronic, Motor Incomplete Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinal Cord Injury
Keywords: Spinal Cord Injuries
4-Aminopyridine
Physical Therapy Modalities
Randomized Controlled Trial
Rehabilitation
Walking
Lead sponsor: Kessler Foundation
Sponsor class: OTHER
Collaborators: name: National Institute on Disability, Independent Living, and Rehabilitation Research
name: Acorda Therapeutics
First posted: 2012-06-18
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy, safety, and tolerability of treatment with dalfampridine in combination with locomotor training in persons with chronic, motor incomplete SCI.

Detailed description: Research suggests that combining therapies could result in important gains in restoring function and improving quality of life in persons with spinal cord injury (SCI). Locomotor training is an activity-dependent rehabilitation therapy that provides repetitive stepping facilitated by manual assistance and body weight support on a treadmill. Recent studies report improvements in walking and standing in individuals with motor incomplete SCI that have undergone intensive standardized locomotor training therapy. Extended release dalfampridine (also known as fampridine or 4-aminopyridine \[4-AP\]) is a broad spectrum potassium channel blocker that has been shown in animal studies to increase conduction of action potentials in demyelinated axons. Dalfampridine was recently approved by the U.S. Food and Drug Administration (FDA) as a treatment to improve walking in persons with multiple sclerosis (MS). Demyelination is also a prominent feature of incomplete SCI that contributes to the clinical presentation of persons with these injuries.

The purpose of this study is to determine the efficacy, safety, and tolerability of treatment with dalfampridine in combination with locomotor training in persons with chronic, motor incomplete SCI. We hypothesize that persons undergoing combination therapy with dalfampridine and locomotor training will show significantly greater improvements in walking speed and other measures of SCI function than those receiving locomotor training alone.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 70 years, inclusive;
* Neurological impairment secondary to a traumatic spinal cord injury that occurred at least twelve (12) months prior to the screening visit;
* Neurological level of the injury between C4 and T10, inclusive;
* The injury is classified as motor incomplete (AIS grade C or D);
* Able and willing to comply with the study protocol, including availability for all scheduled clinic visits and locomotor training sessions.

Exclusion Criteria:

* The participant is a lactating female, or a female of childbearing potential who is sexually active, has not had a hysterectomy or oophorectomy, and is not using an approved birth control method (e.g. tubal ligation, implantable contraception device, oral or injectable contraceptive, barrier method, or sexual activity restricted to vasectomized partner);
* The participant has a history of seizures or treatment for seizure disorders;
* The participant has renal impairment (Creatinine Clearance \< 80 mL/min);
* The participant has a known allergy to pyridine-containing substances or any of the inactive ingredients of the dalfampridine;
* The participant has a clinically significant abnormal laboratory values or an abnormal electrocardiogram (ECG);
* The participant has evidence of significant, diffuse, or generalized lower motor neuron damage;
* The participant has received new concomitant medication less than 3 weeks before the study or has a dose of current concomitant medication that is expected to change during study;
* The participant has received botulinum toxin injection for spasticity within 4 months of the screening visit;
* The participant has taken any other investigational drugs within 30 days before screening;
* The participant is known to have been treated previously with dalfampridine (4 aminopyridine) in any formulation, whether through participation in a previous fampridine study or by self-medication.
* The participant has received locomotor training therapy within 6 months of the screening visit;
* The participant has a history of alcohol or drug abuse in the previous year;
* The participant has a medical condition that would interfere with interpretation of study results or study conduct.

Note: Due to equipment and safety issues associated with locomotor training, participants must weigh less than 300 lbs.

Primary outcomes:
measure: Change in 6-Minute Walk Test (6MWT) Distance at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22) Visits
Secondary outcomes:
measure: Change in 10-Meter Walk Test (10MWT) Speed at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Timed 25-foot walk (T25FW) Speed at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Walking Index for Spinal Cord Injury II (WISCI II) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Spinal Cord Injury Functional Ambulation Index (SCI-FAI) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Changes on International Standards for Neurological Classification of Spinal Cord Injury at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Lower-Extremity Motor Scores (LEMS) at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Berg Balance Scale (BBS) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Modified Ashworth Scale (MAS) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Bowel Management Questionnaire Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Bladder Management Questionnaire Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Female Sexual Function Index (FSFI) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in International Index of Erectile Function (IIEF) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Changes in Pulmonary Function Tests at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Changes in Autonomic Function at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Changes on the International Spinal Cord Injury Pain Basic Data Set (ISCIPDS:B) at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Spinal Cord Independence Measure III (SCIM III) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Spinal Cord Injury-Functional Index (SCI-FI) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in 12-Item Short Form Health Survey (SF-12) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Satisfaction with Life Scale (SWLS) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Craig Handicap Assessment and Reporting Technique (CHART) Scores at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Subject Global Impression (SGI) of Change at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Change in Clinician Global Impression (CGI) of Change at 10 Weeks
timeFrame: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22)
measure: Adverse Event Case Report Form
timeFrame: Every two weeks for 10 weeks
measure: Side Effects Record
timeFrame: Every two weeks for 10 weeks
Other outcomes:
Locations:
city: West Orange
country: United States
facility: Kessler Institute for Rehabilitation
state: New Jersey
Study officials:
affiliation: Kessler Institute for Rehabilitation
name: Steven C. Kirshblum, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kessler Foundation
name: Gail F. Forrest, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kessler Foundation
name: Trevor A. Dyson-Hudson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: