Efficacy of Dalfampridine on Upper Extremity Function in Patients With MS

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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Sustained-release oral dalfampridine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shlomo Noy, MD, PhD; Phone Number: 972-3-5305284; Email: Shlomo.noy@sheba.health.gov.il
• Study Contact Backup: Name: Alon Kalron, PhD; Phone Number: 972-2-2436839; Email: alkalron@gmail.com

Study Locations

• Israel
  • Ramat-gan
    • Tel-hashomer, Ramat-gan, Israel
      • Multiple Sclerosis Center
      • Contact: Alon Kalron, PhD; Phone Number: 972-52-2436839; Email: alkalron@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. The patient must have been diagnosed with clinically definite MS, at the time of informed consent.
3. The patient must be between 18-70 years of age, inclusive, at the time of informed consent.
4. 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:

1. Onset of multiple sclerosis exacerbation within 60 days of screening.
2. History of seizures or evidence of epileptic form activity found on a screened electroencephalogram.
3. Changes in concomitant medications to avoid related changes in multiple sclerosis symptoms during the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental; 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; 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.; Other Names: Ampyra; Prolonged-release Fampridine
Placebo Comparator: Placebo; 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; 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.; Other Names: Active comparator

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Study Director: Anat Achiron, MD, PhD, Multiple Sclerosis Center, Sheba Medical Hospital

Publications and helpful links

General Publications

• Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F203 Investigators. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8. doi: 10.1016/S0140-6736(09)60442-6.
• Judge SI, Bever CT Jr. Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Pharmacol Ther. 2006 Jul;111(1):224-59. doi: 10.1016/j.pharmthera.2005.10.006. Epub 2006 Feb 9.
• van Diemen HA, Polman CH, van Dongen TM, van Loenen AC, Nauta JJ, Taphoorn MJ, van Walbeek HK, Koetsier JC. The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. Ann Neurol. 1992 Aug;32(2):123-30. doi: 10.1002/ana.410320203.
• Stefoski D, Davis FA, Fitzsimmons WE, Luskin SS, Rush J, Parkhurst GW. 4-Aminopyridine in multiple sclerosis: prolonged administration. Neurology. 1991 Sep;41(9):1344-8. doi: 10.1212/wnl.41.9.1344.
• Johansson S, Ytterberg C, Claesson IM, Lindberg J, Hillert J, Andersson M, Widen Holmqvist L, von Koch L. High concurrent presence of disability in multiple sclerosis. Associations with perceived health. J Neurol. 2007 Jun;254(6):767-73. doi: 10.1007/s00415-006-0431-5. Epub 2007 Apr 2.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): November 1, 2014
• Study Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 5, 2014
• First Posted (Estimate): October 8, 2014

Study Record Updates

• Last Update Posted (Estimate): October 8, 2014
• Last Update Submitted That Met QC Criteria: October 5, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: SHEBA-13-0380-AA-CTIL