Efficacy of Dalfampridine on Upper Extremity Function in Patients With MS

Study Overview
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Brief Summary
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This study evaluates the effects of sustained-release oral dalfampridine in the treatment of upper limb deficits in people with multiple sclerosis (MS). In this double-blind randomized pilot study half of participants will dalfampridine, while the other half will receive a placebo.

Detailed Description
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Dalfampridine (ampyra), a drug with a mechanism for symptomatic management of MS among blocks potassium channels on demyelinated neurons, allows normal electrical conduction. Dalfampridine has recently been found to be associated with improvements in visual function, strength, ambulation, fatigue, and endurance in individuals with MS. Although this medication has a widespread effect, its influence on upper extremity function has never been investigated in a double blind randomized case control study. Following the fact that during the disease course, approximately 3 out of 4 multiple sclerosis patients encounter upper limb dysfunction the primary objective of this study will be to investigate the efficacy of sustained-release oral dalfampridine on upper extremity function in patients with MS.

Official Title
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Efficacy of Sustained-release Oral Dalfampridine on Upper Extremity Function in Patients With Multiple Sclerosis: a Pilot Study

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Sustained-release oral dalfampridine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have the ability to understand the purpose and risks of the study provide a signed and dated informed consent and authorize confidential health information to be examined in accordance with national and local subject privacy regulations. The patient must have been diagnosed with clinically definite MS, at the time of informed consent. The patient must be between 18-70 years of age, inclusive, at the time of informed consent. The patient must have scored between 50 and 90 on the upper limb Motricity Index test, at the time of informed consent. This test evaluates strength during three essential movements (pinch grasp, elbow flexion and shoulder abduction). The selected score range criteria determine patients who suffer a moderate decline in function abilities of the upper limb. Exclusion Criteria: Onset of multiple sclerosis exacerbation within 60 days of screening. History of seizures or evidence of epileptic form activity found on a screened electroencephalogram. Changes in concomitant medications to avoid related changes in multiple sclerosis symptoms during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental<br>Intervention: Sustained-release oral dalfampridine, one 10 mg tablet, twice daily, taken 12 hours apart (one tablet in the morning and one tablet in the evening) for 14 consecutive days. | Drug: Sustained-release oral dalfampridine<br>* One Sustained-release oral dalfampridine; 10 mg tablet, twice daily, taken 12 hours apart (one tablet in the morning and one tablet in the evening) taken for 14 consecutive days.<br>* Other names: Ampyra;|
| Placebo Comparator: Placebo<br>Placebo, one 10 mg tablet, twice daily, taken 12 hours apart (one tablet in the morning and one tablet in the evening) for 14 consecutive days. | Drug: Placebo<br>* Placebo, 10 mg tablet, twice daily, taken 12 hours apart (one tablet in the morning and one tablet in the evening) taken for 14 consecutive days.<br>* Other names: Active comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nine-Hole Peg Test | The Nine-Hole Peg Test is a brief, standardized, quantitative test of upper extremity function | Changes in the Nine-Hole Peg Test from Baseline to end of Second week | 
| Nine-Hole Peg Test | The Nine-Hole Peg Test is a brief, standardized, quantitative test of upper extremity function | Changes in the Nine-Hole Peg Test from Baseline to end of first week | 
| Nine-Hole Peg Test | The Nine-Hole Peg Test is a brief, standardized, quantitative test of upper extremity function | Changes in the Nine-Hole Peg Test from end of second week to follow up 2-weeks after end of intervention phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Box and Block test | The box and blocks test (BBT) examines manual dexterity | Changes in the Box and Block Test from Baseline to end of Second week | 
| Box and Block test | The box and blocks test (BBT) examines manual dexterity | Changes in the Box and Block Test from Baseline to end of first week | 
| Box and Block test | The box and blocks test (BBT) examines manual dexterity | Changes in the Box and Block Test from end of second week to follow up 2-weeks after end of intervention phase | 
| Isometric grip force and motor fatigue | Peak isometric grip force (in NM) and isometric fatigue index will be determined by a hand-held dynamometer (Biometrics Ltd., USA). The hand-held dynamometer is a medical device used to assess grip strength in functional assessment and in initial and ongoing evaluation of patients with hand dysfunction | Changes in the Isometric grip force and motor fatigue tests from baseline to end of Second week | 
| Isometric grip force and motor fatigue | Peak isometric grip force (in NM) and isometric fatigue index will be determined by a hand-held dynamometer (Biometrics Ltd.,USA). The hand-held dynamometer is a medical device used to assess grip strength in functional assessment and in initial and ongoing evaluation of patients with hand dysfunction | Changes in the Isometric grip force and motor fatigue tests from baseline to end of first week | 
| Isometric grip force and motor fatigue | Peak isometric grip force (in NM) and isometric fatigue index will be determined by a hand-held dynamometer (Biometrics Ltd.,USA). The hand-held dynamometer is a medical device used to assess grip strength in functional assessment and in initial and ongoing evaluation of patients with hand dysfunction | Changes in the Isometric grip force and motor fatigue tests from end of second week to follow up 2-weeks after end of intervention phase | 
| Sensory evaluation | The two-point discrimination test will be used to determine tactile sensation. Light-touch and pressure-sensation thresholds will be determined using monofilaments | Changes in the Sensory evaluation Test from Baseline to end of Second week | 
| Sensory evaluation | The two-point discrimination test will be used to determine tactile sensation. Light-touch and pressure-sensation thresholds will be determined using monofilaments | Changes in the Sensory evaluation Test from Baseline to end of first week | 
| Sensory evaluation | The two-point discrimination test will be used to determine tactile sensation. Light-touch and pressure-sensation thresholds will be determined using monofilaments | Changes in the Sensory evaluation Test from end of second week to follow up 2-weeks after end of intervention phase | 
| Patient rating scale - Disabilities of the Arm, Shoulder and Hand (DASH) | The DASH (http://www.dash.iwh.on.ca/) has 30 items grouped into one scale aiming to measure 'physical function and symptoms' in people with disorders of the upper limb.15 Items are scored from 1 (no difficulty) to 5 (unable). A total 'disability/symptom' score is generated by summing items, and averaging to produce a mean item score between 1 and 5 | Changes in the DASH Test from Baseline to end of Second week | 
| Patient rating scale - Disabilities of the Arm, Shoulder and Hand (DASH) | The DASH (http://www.dash.iwh.on.ca/) has 30 items grouped into one scale aiming to measure 'physical function and symptoms' in people with disorders of the upper limb.15 Items are scored from 1 (no difficulty) to 5 (unable). A total 'disability/symptom' score is generated by summing items, and averaging to produce a mean item score between 1 and 5 | Changes in the DASH Test from Baseline to end of first week | 
| Patient rating scale - Disabilities of the Arm, Shoulder and Hand (DASH) | The DASH (http://www.dash.iwh.on.ca/) has 30 items grouped into one scale aiming to measure 'physical function and symptoms' in people with disorders of the upper limb.15 Items are scored from 1 (no difficulty) to 5 (unable). A total 'disability/symptom' score is generated by summing items, and averaging to produce a mean item score between 1 and 5 | Changes in the DASH Test from end of second week to follow up 2-weeks after end of intervention phase |