Dalfampridine for Imbalance in Multiple Sclerosis

Dalfampridine to Improve Imbalance in Multiple Sclerosis: A Pilot Study

Dalfampridine is a new medication that was FDA approved in 2010 to improve walking speed in people with Multiple Sclerosis (MS). People with MS walk slowly in part because MS damages the myelin insulation around nerves which slows conduction of messages from the brain to the leg muscles. Dalfampridine works by improving conduction in nerves with damaged myelin. Recent research indicates that imbalance in MS is in large part caused by poor conduction by the nerves that transmit information about the position of the legs to the brain. It is therefore likely that, by improving nerve conduction, dalfampridine will also improve imbalance in people with MS. Dalfampridine will be administered in this study by the same route (oral), dosage (10mg), and frequency (every 12 hours) approved by the FDA to improve walking speed in people with MS. The proposed pilot study will examine the effects of dalfampridine on imbalance in 24 subjects with Multiple Sclerosis (MS) and imbalance. This small pilot study will help to show if dalfampridine improves imbalance in MS and will guide the design and implementation of a larger full scale study to definitively determine if dalfampridine improves balance and prevents falls in people with MS.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Fatigue
• Intervention / Treatment: Drug: Dalfampridine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 20- 59 years,
• Able to walk at least 100m without an aide or with unilateral assistance
• Prolonged APR latencies (≥ 1SD > mean for healthy people in this age range) OR,
• Reduced balance-related activity (ABC scores ≤ 85%),
• Abnormal trunk range of motion (horizontal), trunk range of motion (frontal), turning duration, cadence, double support time, stride length or gait cycle time (outside 1SD of the average for healthy people in this age range)

Exclusion Criteria:

• Currently taking dalfampridine (any within the last 2 weeks),
• Cause(s) of imbalance other than MS,
• Impaired renal function (creatinine clearance ≤50mL/min),
• Seizure disorder
• Pregnancy or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; placebo pill, bid for 12 weeks
Experimental: Dalfampridine	Drug: Dalfampridine; 10mg, bid, pill taken by mouth for 12 weeks; Other Names: Ampyra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Automatic Postural Response (APR )Latency	Automatic Postural Response (APR) latencies will be measured by Computerized Dynamic Posturography (CDP). The restoration of balance after an unexpected movement by Computerized Dynamic Posturography relies on automated postural responses in the upper and lower legs, trunk, shoulders, and neck muscles. APR latency is the reaction- time response to movements of the support surface on which the subject stands. These responses typically occur at onset latencies of ~100 milliseconds. In response to a change, both feet-in-place and stepping strategies can be used to recover balance, with the incidence of stepping responses becoming larger as the change magnitude increases voluntary movements in human subjects.	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores	The ABC is an 11-point scale and subjects are asked to indicate personal level of confidence in doing specific activities without losing balance or becoming unsteady on a scale from 0% to 100%. The ratings are added (possible range =0 -1600) and divide by 16 to get each subject's ABC score. A high ABC score indicates a high degree of confidence and a low ABC score indicates a low degree of confidence.	Baseline to 12 weeks
Change in Timed 25 Foot Walking Speed		Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Acorda Therapeutics

Publications and helpful links

Helpful Links

• OHSU Multiple Sclerosis Center

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 29, 2011
• First Posted (Estimate): September 30, 2011

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: May 16, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: fatigue; gait; multiple sclerosis; postural balance
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: GNEUR0637A