Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02208050
Recruitment Status : Completed
First Posted : August 4, 2014
Results First Posted : July 9, 2021
Last Update Posted : July 9, 2021
Sponsor:
Information provided by (Responsible Party):
Christopher McGuigan, University College Dublin

Brief Summary:

The purpose of this study is to examine the effect of treatment with fampridine in patients with secondary progressive MS (SPMS) or primary progressive MS (PPMS) with upper limb dysfunction (as defined by a 9-HPT time of between 15-90 seconds) and Kurtzke EDSS scores in the range 4.0-7.0 on upper limb function assessed by the nine-hole peg test (9-HPT) and the Jebson Taylor Hand Function Test (JTT).

Fampridine has been shown to be effective in improving motor function, specifically walking ability in prior studies in this patient population and is currently licensed for this use in Europe and the United States. Upper limb dysfunction is common in SPMS and PPMS and often underestimated. Fampridine effects action potential conduction in demyelinated nerve fibres and we would hypothesise that the improvement previously reported in walking ability would be similar to that on upper limb dysfunction. Our study aims to address this question using both independent and patient reported outcomes in the context of a randomised placebo controlled crossover trial.


Condition or disease Intervention/treatment Phase
Secondary Progressive Multiple Sclerosis Primary Progressive Multiple Sclerosis Drug: Fampridine Drug: Placebo Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IV Double Blind, Randomized, Placebo Controlled, Crossover Study of the Effectiveness of Oral Fampridine in Improving Upper Limb Function in Progressive Multiple Sclerosis
Actual Study Start Date : February 21, 2014
Actual Primary Completion Date : February 16, 2016
Actual Study Completion Date : February 16, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Group 1
Patients will be randomised to a 8 week treatment period with the active drug followed by a 2 week washout period before an 8 week treatment period with placebo.
Drug: Fampridine
Other Name: Fampyra

Drug: Placebo
Group 2
Patients will be randomised to a 8 week treatment period with the placebo, followed by a 2 week washout period and a further 8 week treatment period with the active drug.
Drug: Fampridine
Other Name: Fampyra

Drug: Placebo



Primary Outcome Measures :
  1. Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT) [ Time Frame: 20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period. ]
    9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two "on treatment" 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 & 5 or 7 & 8) improving 20% from the average of the baseline assessments (1, 2 & 3). Washout assessment not included in the analysis.


Secondary Outcome Measures :
  1. Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT) [ Time Frame: 20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8 ]

    Jebsen Taylor Hand Function Test (JTT) is a timed test (seconds) comprising of seven 'real-world' tasks such as picking up small items. It has been validated for use in upper limb function in MS. A secondary measure of upper limb responsiveness will be defined as number of participants with a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebsen Taylor Hand Function Test "on treatment" (assessments 4 & 5 or 7 & 8) compared with baseline assessments (assessments 1,2 & 3).

    Baseline assessments (1,2,3) performed in two week period prior to first treatment block. Longer time indicates worse functioning. Improvement is defined as shorter time in seconds.

    Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period


  2. The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW) [ Time Frame: 20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8 ]

    A mobility responder to Fampridine will be defined as a patient with both of the two "on treatment" T25FW assessments (assessments 4 & 5 or 7 & 8) being better (shorter time in seconds) than the maximum of any of the four "off treatment" assessments (assessments 1, 2, 3, 6). Otherwise the patient will be deemed a non-responder. T25FW test is the time taken to walk 25 feet taken as the average of two trials. Measured in seconds. Longer time indicates slower walking. Improvement is considered shorter amount of time in seconds - no specific percentage or amount of time was considered necessary.

    Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period.


  3. Mean Scores in DASH - Fampridine and Placebo. [ Time Frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period. ]

    Disabilities of the Arm Shoulder and Hand Scores questionnaire: The DASH consists of a 30-item disability symptom scale scored 0 (no disability) to 100, developed as a self-rated upper extremity disability and symptoms. Higher scores indicate higher self-perception of disability.

    DASH questionnaire administered to fampridine treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged. DASH questionnaire administered to placebo treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged.


  4. Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo. [ Time Frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period. ]
    Multiple Sclerosis Walking Scale 12 is a 12-item self report measure of the impact of MS on an individual's walking ability. Scores are summed 1-3; 1-5 for each item. Higher scores indicate higher limitation in walking ability. Scores are summed and transformed to a 0-100 scale again with higher scores indicating higher self-reported limitation in walking ability. MSWS12 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. MSWS-12 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.

  5. Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo. [ Time Frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period. ]
    AMSQ - Arm Function in Multiple Sclerosis Questionnaire. This is a 31-item patient reported outcome measure which is validated to measure limitation in arm and hand functioning in people with multiple sclerosis. Patients rate the ability to which they can perform routine daily tasks with current hand function. Higher scores indicate greater limitations. Scale ranges from 0-100. AMSQ scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. AMSQ scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.

  6. Mean Scores of MSIS-29 - Fampridine and Placebo [ Time Frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period. ]
    MSIS-29 is a patient reported outcome with a physical and psychological component combined into one scale. They refer to the self-reported impact of MS on their physical and psychological wellbeing. Higher scores indicate a higher impact on functioning. The 20 item physical scale and the 9 item psychological scale are reported as two separate scaled scores. Both scale ranges are 0-100. Higher scores indicate a higher impact on functioning. MSIS -20 and MSIS-9 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the scores was averaged. MMSIS-20 and MSIS-9 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the scores was averaged.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
  • Subjects must be diagnosed with clinically definite SPMS or PPMS and be judged to be in generally good health by the investigator based upon the results of the medical history, laboratory tests (liver and renal function), physical examination, 12-lead electrocardiogram performed during Screening
  • Subjects must be Male or female aged 18-70 at baseline
  • Kurtzke EDSS scores in the range 4.0 to 7.0 inclusive
  • Evidence of significant upper limb dysfunction as defined by a 9HPT of 15 - 90 seconds (dominant or non-dominant hand)
  • Female subjects with reproductive capabilities must have a negative serum pregnancy test at baseline and agree to using an acceptable form of contraception for the duration of the study (barrier, coil or oral contraceptives only).

Exclusion Criteria:

  • Allergy/sensitivity to study medications or their ingredients
  • Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study.
  • Subjects unable to provide written informed consent
  • Subjects with a history of epilepsy or previous seizures (including provoked seizures).
  • Subjects who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements.
  • Subjects with an AST or ALT ≥ 3 x ULN on liver function tests
  • Subjects have clinically significant ECG findings as judged by the investigator, in particular evidence of a cardiac conduction defect.
  • Significant upper or lower limb arthritis as considered by the investigator to interfere with study assessments.
  • Significant cognitive impairment as considered by the investigator to interfere with study assessments
  • Subjects with clinically significant upper limb ataxia considered by the investigator to interfere with ability to complete study outcome measures.
  • Patients with mild, moderate or severe renal impairment (creatinine clearance<80ml/min) measured by 24-hour urine collection or estimated by the Cockcroft and Gault formula
  • Subjects concomitantly using medicinal products that are inhibitors of Organic Cation Transporter 2 (OCT2) for example cimetidine
  • Concurrent treatment with other medicinal products containing fampridine (4- aminopyridine)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02208050


Locations
Layout table for location information
Ireland
St Vincent's University Hospital
Dublin, Dublin 4, Ireland
St. Vincents University Hospital
Dublin, Ireland, D4
Sponsors and Collaborators
University College Dublin
Investigators
Layout table for investigator information
Principal Investigator: Christopher McGuigan, MD University College Dublin, St Vincent's University Hospital
  Study Documents (Full-Text)

Documents provided by Christopher McGuigan, University College Dublin:
Layout table for additonal information
Responsible Party: Christopher McGuigan, Consultant Neurologist, University College Dublin
ClinicalTrials.gov Identifier: NCT02208050    
Other Study ID Numbers: SVUHneuro002
First Posted: August 4, 2014    Key Record Dates
Results First Posted: July 9, 2021
Last Update Posted: July 9, 2021
Last Verified: July 2021
Keywords provided by Christopher McGuigan, University College Dublin:
Secondary Progressive Multiple Sclerosis
Primary Progressive Multiple Sclerosis
Multiple Sclerosis
Upper limb function
Mobility
Fampridine
DASH
AMSQ
MSWS-12
MSIS-29
SF-36
9HPT
25FTW
JTT
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
4-Aminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action