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Safety and Efficacy of Sustained Release Dalfampridine in Transverse Myelitis (Re-Launch)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Acorda Therapeutics
Information provided by (Responsible Party):
Michael Levy, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT02166346
First received: June 16, 2014
Last updated: December 20, 2016
Last verified: December 2016
  Purpose

Transverse myelitis (TM) is an inflammatory disorder of the spinal cord that leads to disabilities of gait. Dalfampridine, a sustained-release potassium inhibitor has been shown to be effective in improving gait and other neurologic functions in multiple sclerosis. Dalfampridine has the potential to improve neurologic function in patients with transverse myelitis as this rare disorder shares a similar pathogenic process with multiple sclerosis. The in a clinical trial to test the efficacy of dalfampridine in TM.

The clinical trial that the investigators propose to conduct will focus on TM and will evaluate the dalfampridine in primary neurologic outcome, 25-foot timed walk, and several secondary outcomes including valid behavioral and neurophysiological tests.

This is a re-launch of the previous trial, which now includes additional behavioral and clinical testing.


Condition Intervention Phase
Transverse Myelitis
Neuromyelitis Optica
Idiopathic Transverse Myelitis
Myelitis NOS
Drug: Dalfampridine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled Crossover Trial on the Safety and Efficacy of Sustained-Release Dalfampridine in Transverse Myelitis (Re-Launch)

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Timed 25-foot walk [ Time Frame: Every 2 weeks for 26 weeks ]
    Timed 25-foot walking trials will be assessed every 2 weeks while on therapy as the primary outcome. The Timed 25 foot walk is a quantitative measure of lower extremity function.


Secondary Outcome Measures:
  • Transcranial magnetic stimulation [ Time Frame: Four times over the course of 26 weeks ]
    This measure will be used as an indicator of the health of the tract in terms of neuronal conduction. To be done at beginning and end of each arm of the study for a total of 4 measures.

  • Lower extremity muscle strength measurements [ Time Frame: Four times over the course of 26 weeks ]
    Lower extremity muscle strength measurements, using a hand held dynamometer, at the beginning and end of each arm.

  • Expanded Disability Severity Scale [ Time Frame: Four times over the course of 26 weeks ]
    A standardized measure of disability used commonly in multiple sclerosis and related disorders done at the beginning and end of each arm.


Estimated Enrollment: 25
Study Start Date: February 2014
Estimated Study Completion Date: May 2017
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dalfampridine
All subjects will be randomized for the first double-blinded 8-week part of the study with 25-foot timed walking assessments every 2 weeks. Then subjects will be crossed over to the other therapy (drug or placebo) for another 8 weeks.
Drug: Dalfampridine
Dalfampridine 10 mg twice daily for 8 weeks
Other Name: Ampyra
Placebo Comparator: Placebo
Placebo controlled arm.
Drug: Placebo
Placebo pill 1 tablet twice daily for 8 weeks
Other Name: Sugar pill

Detailed Description:

Fampridine (4-aminopyridine) is a potassium channel blocker that has been studied since the 1970s for its effect on amplifying conductivity in peripheral nerves, potentiating neurotransmitter release in muscles and increasing post-synaptic action potentials in the spinal cord. It was tested in other neurologic conditions over the next two decades and was found to have a limited therapeutic window due to the stimulation of seizures at high doses. The first randomized, placebo-controlled, double-blinded study of fampridine in 70 patients found significant improvements in a number of neurophysiological parameters while on fampridine compared to placebo. Since then, at least six additional studies on oral fampridine in MS were conducted and found to have some significant neurologic function. Although only a small incidence of seizure or altered mental status were reported in these studies, the concern about fampridine causing seizures remained a barrier in the acceptance of fampridine as an MS therapy in the general neurology community.

Recently, Biogen-Idec and Acorda have teamed up in the development of a sustained-release formulation of fampridine, dalfampridine, in which plasma concentrations of the drug and avoids toxic doses that lead to seizures. In two clinical trials, dalfampridine has been shown to be beneficial in two large cohorts of multiple sclerosis patients with noted improvements in gait and lower extremity muscle strength. Seizures were only seen in high doses of 20 mg or more whereas benefits were evident at the approved dose of 10 mg twice daily.

The Food and Drug Administration (FDA) approved dalfampridine for use in multiple sclerosis in 2009 based on the key study that evaluated gait by timed 25-foot walk. About 35-40% of study participants responded and this group improved their walking speed by about 20%.

The investigator's interest in dalfampridine is focused more narrowly on a subset of patients with a demyelinating disorder that is restricted to the spinal cord, transverse myelitis (TM), was not included in any previous human trials of dalfampridine. In contrast to MS, which affects the entire system, transverse myelitis affects the spinal cord and largely spares the brain. It is not associated with an increased risk of seizure.

Transverse myelitis is defined as an episode of inflammation in the spinal cord leading to disability at the level of the lesion and below. The majority of TM lesions strike the thoracic cord causing impairments in lower extremities. A single lesion is the cause of all of their symptoms. The goal of using dalfampridine in these patients is to amplify axonal conductance across the lesion. This would manifest as improved neurologic function involving the lower extremities including gait. This is a straightforward proof of concept model proving the mechanism of action of dalfampridine.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of transverse myelitis confirmed by MRI
  2. Gait impairment defined as a baseline timed 25-foot walk of at least 5 seconds and no more than 60 seconds.
  3. Age 18-70.

Exclusion Criteria:

  1. Diagnosis of any of the following concurrent conditions: spinal dural arteriovenous malformation, multiple sclerosis, infectious myelitis and recurrent transverse myelitis of any etiology. Subjects with a positive NMO-IgG biomarker test will be permitted to join the study as long as the there is only a history of monophasic, and not recurrent, TM.
  2. History of seizure(s).
  3. Pregnancy or positive pregnancy test (mandatory test for all women aged 18-55 to be done at first screening visit).
  4. Known use or allergy to dalfampridine or any other formulation of 4-aminopyridine.
  5. Patients unable to walk.
  6. Patients with history of severe alcohol or drug abuse, severe psychiatric illness such as severe depression, poor motivational capacity, or severe language disturbances, particularly of receptive nature or with serious cognitive deficits (defined as equivalent to a mini-mental state exam score of 23 or less).
  7. Patients with severe uncontrolled medical problems (e.g. hypertension, cardiovascular disease, severe rheumatoid arthritis, active joint deformity of arthritic origin, active cancer or renal disease, any kind of end-stage pulmonary or cardiovascular disease, claudication, uncontrolled epilepsy or others).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02166346

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Acorda Therapeutics
Investigators
Principal Investigator: Michael Levy, MD, PhD Johns Hopkins University
  More Information

Responsible Party: Michael Levy, Assistant Professor, Neurology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02166346     History of Changes
Obsolete Identifiers: NCT01446575
Other Study ID Numbers: AMPYRA-TM-2
Study First Received: June 16, 2014
Last Updated: December 20, 2016

Keywords provided by Johns Hopkins University:
Transverse myelitis

Additional relevant MeSH terms:
Myelitis
Myelitis, Transverse
Neuromyelitis Optica
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases
Central Nervous System Infections
Central Nervous System Diseases
Spinal Cord Diseases
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Paraneoplastic Syndromes
Neurodegenerative Diseases
4-Aminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017