Combination Therapy With Dalfampridine and Locomotor Training for Chronic, Motor Incomplete Spinal Cord Injury

NCT ID: NCT01621113

Last Updated: 2017-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2017-10-16

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.

Conditions

Spinal Cord Injury

Keywords

Spinal Cord Injuries; 4-Aminopyridine; Physical Therapy Modalities; Randomized Controlled Trial; Rehabilitation; Walking

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Dalfampridine

Intervention Type: DRUG

Dalfampridine 10 mg tablet, twice-daily, for 10 weeks

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablet, twice daily, for 10 weeks.

Interventions

Dalfampridine

Dalfampridine 10 mg tablet, twice-daily, for 10 weeks

Intervention Type: DRUG

Placebo

Placebo tablet, twice daily, for 10 weeks.

Intervention Type: DRUG

Other Intervention Names

Ampyra; Fampridine Sustained Release (Fampridine-SR); 4-Aminopyridine (4-AP)

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Disability, Independent Living, and Rehabilitation Research

FED

Sponsor Role: collaborator

Acorda Therapeutics

INDUSTRY

Sponsor Role: collaborator

Kessler Foundation

OTHER

Sponsor Role: lead

Responsible Party

Trevor Dyson-Hudson, M.D.

Director, Spinal Cord Injury Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven C. Kirshblum, M.D.

Role: PRINCIPAL_INVESTIGATOR

Kessler Institute for Rehabilitation

Gail F. Forrest, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Kessler Foundation

Trevor A. Dyson-Hudson, M.D.

Role: PRINCIPAL_INVESTIGATOR

Kessler Foundation

Locations

Kessler Institute for Rehabilitation

West Orange, New Jersey, United States

Countries

United States

Other Identifiers

H133N110020

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

D-732-12

Identifier Type: -

Identifier Source: org_study_id