Restoring Lost Functions After Spinal Cord Injury: Combination Therapy With Dalfampridine and Locomotor Training for Persons With Chronic, Motor Incomplete Spinal Cord Injury
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Change in 6-Minute Walk Test (6MWT) Distance at 10 Weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Locomotor Training + Dalfampridine
Subjects randomized to this group will undergo 10 weeks of double-blind treatment with extended release dalfampridine tablets (10 mg twice daily) while simultaneously receiving locomotor training therapy (5 sessions per week x 10 weeks = 50 sessions total).
干预措施: Dalfampridine (Drug)
Locomotor Training + Placebo
Subjects randomized to this group will undergo identical treatment, but will take placebo tablets while simultaneously receiving locomotor training therapy (5 sessions per week x 10 weeks = 50 sessions total).
干预措施: Placebo (Drug)
结局指标
主要结局
Change in 6-Minute Walk Test (6MWT) Distance at 10 Weeks
时间窗: Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22) Visits
The 6MWT measures the distance (in meters) walked within 6 minutes. The test is a measure of endurance; however, can also be used to measure walking speed.
次要结局
- Change in 10-Meter Walk Test (10MWT) Speed at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Timed 25-foot walk (T25FW) Speed at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Walking Index for Spinal Cord Injury II (WISCI II) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Spinal Cord Injury Functional Ambulation Index (SCI-FAI) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Changes on International Standards for Neurological Classification of Spinal Cord Injury at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Lower-Extremity Motor Scores (LEMS) at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Berg Balance Scale (BBS) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Modified Ashworth Scale (MAS) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Bowel Management Questionnaire Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Bladder Management Questionnaire Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Female Sexual Function Index (FSFI) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in International Index of Erectile Function (IIEF) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Changes in Pulmonary Function Tests at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Changes in Autonomic Function at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Changes on the International Spinal Cord Injury Pain Basic Data Set (ISCIPDS:B) at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Spinal Cord Independence Measure III (SCIM III) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Spinal Cord Injury-Functional Index (SCI-FI) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in 12-Item Short Form Health Survey (SF-12) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Satisfaction with Life Scale (SWLS) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Craig Handicap Assessment and Reporting Technique (CHART) Scores at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Subject Global Impression (SGI) of Change at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Change in Clinician Global Impression (CGI) of Change at 10 Weeks(Baseline, Mid-Point (Week 5), Final (Week 10), and Follow-up (Week 22))
- Adverse Event Case Report Form(Every two weeks for 10 weeks)
- Side Effects Record(Every two weeks for 10 weeks)
研究者
Trevor Dyson-Hudson, M.D.
Director, Spinal Cord Injury Research
Kessler Foundation