This trial has now closed.

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.

Inclusion Criteria

• 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.
• EDSS 4.0-6.5

Patient Exclusions

• 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.

If you require any help, please contact: Raj Kapoor (Chief Investigator) Email: raj.kapoor@uclh.nhs.uk

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