Safety and Efficacy of Sustained Release Dalfampridine in Transverse Myelitis (Re-Launch)
Condition: Transverse Myelitis; Neuromyelitis Optica; Idiopathic Transverse Myelitis; Myelitis NOS
MeSH terms: Myelitis; Myelitis, Transverse; Neuromyelitis Optica
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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 Multiple Sclerosis (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.
    

Intervention name(s): Dalfampridine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Dalfampridine 10 mg twice daily for 8 weeks; Placebo pill 1 tablet twice daily for 8 weeks
Other intervention name(s): Ampyra; Sugar pill
Intervention MeSH terms: 4-Aminopyridine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Transverse myelitis