This trial has now closed and the results
in the Lancet Neurology 2010.
A double blind parallel group randomised controlled trial of neuroprotection with lamotrigine in secondary progressive multiple sclerosis.
At present, there is no safe, widely applicable treatment that is capable of
reducing the rate at which disability advances in secondary progressive
multiple sclerosis (SPMS). There is good evidence that the primary cause of
disability is axonal degeneration within the CNS, so there is considerable
interest in developing treatments which can protect axons from degeneration.
Experimental work by members of our group has established that axons may
degenerate upon exposure to the inflammatory mediator nitric oxide. The
mechanism of the damage implies that protection might be afforded by the novel
approach of partially blocking sodium channels, and our group and others have
recently demonstrated that drugs including flecainide, phenytoin and
lamotrigine can reduce axonal degeneration when optic nerves or spinal roots
are exposed to nitric oxide, and in experimental autoimmune encephalomyelitis.
Age 18-60 years
Men and women will be included, but women of childbearing age would be
required to use appropriate methods of contraception to avoid any teratogenic
effects of lamotrigine.
Patients with a diagnosis of SPMS where steady progression rather than relapse
is the major cause of increased disability in the preceding 2 years.
Evidence of progression can be from either
1) clinical documentation of steadily increasing disability, or 2) an increase of at
least 1 point in EDSS measurements.
SPMS with very rapid deterioration of disability, if eligible for treatment
with mitoxantrone at one of our Centres (the National Hospital for Neurology
and Neurosurgery) using a protocol recently approved by the Trust's
Pharmaceutical Committee, making it unethical to offer an alternative,
experimental treatment in a clinical trial.
Use of Na+ or Ca2+ channel blockers in the previous 2 weeks, corticosteroids
in the previous 2 months, mitoxantrone in the previous year, or other
immunosuppressive drugs in the previous 6 months.
Evidence of significant hepatic or renal abnormalities, either in the
clinical history or in blood tests prior to entry into the trial. Patients
with other major systemic diseases will also be excluded.
Past untoward reactions to lamotrigine, or disabling temperature-dependent
symptoms related to MS.
Contraindications to MR imaging.
Randomisation service provided by: Sealed Envelope.com