Dalfampridine for Imbalance in Multiple Sclerosis

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01444300
• Collaborator: Acorda Therapeutics (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis; Fatigue	Drug: Dalfampridine; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dalfampridine to Improve Imbalance in Multiple Sclerosis: A Pilot Study
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Automatic Postural Response (APR )Latency [Baseline to 12 weeks]

   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.

Secondary Outcome Measures

1. Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores [Baseline to 12 weeks]

   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.

2. Change in Timed 25 Foot Walking Speed [Baseline to 12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 59 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health and Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University
• Acorda Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• OHSU Multiple Sclerosis Center

Publications

None provided.

• Responsible Party: Michelle Cameron, Principal Investigator, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01444300
• Other Study ID Numbers: GNEUR0637A
• First Posted: Sep 30, 2011
• Last Update Posted: Jun 16, 2014
• Last Verified: May 1, 2014

• Keywords provided by Michelle Cameron, Principal Investigator, Oregon Health and Science University: multiple sclerosis; postural balance; gait; fatigue
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Fatigue; 4-Aminopyridine

Study Results

Participant Flow

Recruitment Details	People with MS were recruited from several MS clinics in the Portland, OR metro area from September 2011 to August 2013. 24 subjects signed the consent and were enrolled in the study.

Arm/Group Title	Dalfampridine	Placebo
Arm/Group Description	Dalfampridine: 10mg, twice daily, pill taken by mouth for 12 weeks	Placebo: placebo pill, twice daily, for 12 weeks
Period Title: Overall Study
STARTED	12	12
COMPLETED	8	12
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Dalfampridine	Placebo	Total
Arm/Group Description	Dalfampridine: 10mg, twice daily (bid), pill taken by mouth for 12 weeks	Placebo: placebo pill, twice daily (bid), for 12 weeks	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.2 (8.9)	47.8 (10.9)	47.5 (9.7)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	6 50%	11 45.8%
Male	7 58.3%	6 50%	13 54.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 8.3%	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 8.3%	1 4.2%
White	11 91.7%	10 83.3%	21 87.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 8.3%	0 0%	1 4.2%
MS Subtype (participants) [Number]
Relapsing Remitting MS (RRMS)	12 100%	8 66.7%	20 83.3%
Secondary Progressive MS (SPMS)	0 0%	2 16.7%	2 8.3%
Primary Progressive MS (PPMS)	0 0%	2 16.7%	2 8.3%

Outcome Measures

1. Primary Outcome

Title	Change in Automatic Postural Response (APR )Latency
Description	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dalfampridine	Placebo
Arm/Group Description	Dalfampridine: 10mg, twice daily (bid), pill taken by mouth for 12 weeks	Placebo: placebo pill, twice daily (bid), pill taken by mouth for 12 weeks
Measure Participants	8	12
Mean (Standard Deviation) [milliseconds]	5.71 (16.2)	4.58 (23.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine, Placebo
	Comments	t test comparing change in outcome between active and placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Activities-specific Balance Confidence (ABC) Questionnaire Scores
Description	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dalfampridine	Placebo
Arm/Group Description	Dalfampridine: 10mg, twice daily (bid), pill taken by mouth for 12 weeks	Placebo: placebo pill, twice daily (bid), pill taken by mouth for 12 weeks
Measure Participants	8	12
Mean (Standard Deviation) [Scores on a scale]	1.30 (9.02)	0.41 (10.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine, Placebo
	Comments	t test comparing change in outcome between active and placebo after 12 weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change in Timed 25 Foot Walking Speed
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dalfampridine	Placebo
Arm/Group Description	Dalfampridine: 10mg, twice daily (bid), pill taken by mouth for 12 weeks	Placebo: placebo pill, twice daily (bid), pill taken by mouth for for 12 weeks
Measure Participants	8	12
Mean (Standard Deviation) [seconds]	0.26 (0.78)	0.39 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine, Placebo
	Comments	t test comparing change in outcome between active and placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	Dalfampridine		Placebo
Arm/Group Description	Dalfampridine: 10mg, twice daily, pill taken by mouth for 12 weeks		Placebo: placebo pill, twice daily, for 12 weeks
All Cause Mortality
	Dalfampridine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dalfampridine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Dalfampridine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/12 (75%)		10/12 (83.3%)
Gastrointestinal disorders
Nausea	5/12 (41.7%)	5	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness	2/12 (16.7%)	2	6/12 (50%)	6
Balance problems	2/12 (16.7%)	2	4/12 (33.3%)	4
Nervous system disorders
Insomnia	4/12 (33.3%)	4	0/12 (0%)	0
Dizziness	3/12 (25%)	3	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Itching/skin reactions	1/12 (8.3%)	1	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.