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A Double Blind, Randomized, Placebo Controlled, Crossover Study of the Effectiveness of Oral Fampridine in Improving Upper Limb Function in Progressive Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT02208050
Recruitment Status : Completed
First Posted : August 4, 2014
Last Update Posted : August 28, 2018
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 Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 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
Study Start Date : March 2014
Actual Primary Completion Date : July 2018
Actual Study Completion Date : July 2018

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
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
Drug: Placebo



Primary Outcome Measures :
  1. The primary end point will be the number of participants who show an improvement of 20% on the 9 Hole Peg Test (9-HPT) at the end of their treatment period with fampridine. These will be classified as upper limb responders. [ Time Frame: 8 week treatment periods ]
    An upper limb responder is defined as a patient with both of the two "on treatment" 9-HPT assessments measured in seconds (assessments 4 & 5 or 7 & 8) improving 20% from the average of the baseline assessments (1, 2 & 3).


Secondary Outcome Measures :
  1. The number of upper limb responders as defined by a 20% improvement in the Jebson Taylor Hand Function Test (JTT) "on treatment" compared to baseline assessments. [ Time Frame: 22 weeks ]
    A secondary measure of upper limb responsiveness will be defined as a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebson Taylor Hand Function Test "on treatment" (assessments 4 & 5 or 7 & 8) compared with baseline assessments (assessments 1,2 & 3).

  2. The number of mobility responders to fampridine as measured by an improvement in the 25 foot timed walk (T25FW) "on treatment" compared to "off treatment". [ Time Frame: 22 weeks ]
    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 than the maximum of any of the four "off treatment" assessments (assessments 1, 2, 3, & 9). Otherwise the patient will be deemed a non-responder.

  3. To compare the change in the Disabilities in Arm, Shoulder and Hand (DASH) score from baseline to end of treatment (either week 10 or week 20) between upper limb responders and non-responders. [ Time Frame: 22 weeks ]
    Upper limb responders as measured by changes in the 9-HPT and/or JTT will be compared to non-responders in relation to the change in the DASH between baseline assessment and end of treatment (week 10 or 20).

  4. Assessment of placebo effect versus treatment effect. [ Time Frame: 22 weeks ]
    Upper limb response will be examined at the end of treatment phase 1 and repeated at the end of the trial by comparing patients receiving active drug with those receiving placebo to assess any placebo effect and allow assessment of any residual beneficial effect on those who receive fampridine in treatment phase 1 and then switch to placebo in treatment phase 2. Response will again be considered as a 20% improvement in the 9HPT in the active treatment group compared with placebo and a 20% improvement from baseline in the time taken to complete all seven tasks in the JTT. See earlier comment

  5. To compare the change in Multiple Sclerosis Walking Scale (MSWS-12) from baseline to end of treatment (either week 10 or week 20) between mobility responders and non-responders. [ Time Frame: 22 weeks ]
    Mobility responders as measured by change in T25FW will be compared to non-responders in relation to the change in the MSWS-12 between baseline assessment and end of treatment (week 10 or 20).

  6. To asses differences in self reported quality of life as measured by the SF-36 from baseline to end of treatment (week 10 or 20) in either upper limb or mobility responders compared to non-responders to treatment. [ Time Frame: 22 weeks ]
    The patients' scores on the SF-36 will be examined in relation to the objective changes (responder/non-responder) in the 9-HPT, JTT and the T25FW.

  7. To compare the change in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) score from baseline to end of treatment (either week 10 or week 20) between upper limb responders and non-responders. [ Time Frame: 22 weeks ]
    Upper limb responders as measured by changes in the 9-HPT and/or JTT will be compared to non-responders in relation to the change in the AMSQ between baseline assessment and end of treatment (week 10 or 20).

  8. To asses differences in self reported measure of disease state by the Multiple Sclerosis Impact Scale (MSIS-29) from baseline to end of treatment (week 10 or 20) in either upper limb or mobility responders compared to non-responders to treatment. [ Time Frame: 22 weeks ]
    Compare changes in MSIS-29 between baseline and end of treatment in either upper limb or mobility responders to fampridine.



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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
Ireland
St Vincent's University Hospital
Dublin, Dublin 4, Ireland
St. Vincents University Hospital
Dublin, Ireland, D4
Sponsors and Collaborators
University College Dublin
Investigators
Principal Investigator: Christopher McGuigan, MD University College Dublin, St Vincent's University Hospital

Responsible Party: Christopher McGuigan, Consultant Neurologist, University College Dublin
ClinicalTrials.gov Identifier: NCT02208050     History of Changes
Other Study ID Numbers: SVUHneuro002
First Posted: August 4, 2014    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018

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:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
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