A Randomised Controlled Trial of Neuroprotection With Lamotrigine in S

A Randomised Controlled Trial of Neuroprotection With Lamotrigine in Secondary Progressive Multiple Sclerosis: Single Centre, Phase 2 Trial

CompletedPhase 2Progressive MSNCT002578552005-001949-42

What it found

Missed its main goal

The main measure did not show a significant benefit.

“The mean change in partial (central) cerebral volume per year was -3.18 mL (SD -1.25) in the lamotrigine group and -2.48 mL (-0.97) in the placebo group (difference -0.71 mL, 95% CI -2.56 to 1.15; p=0.40).”
Read by software from the paper's abstract

rate of change of partial (central) cerebral volume over 24 months · 24 months

GroupnValue
lamotrigine61-3.18 mL (SD -1.25) per year
placebo59-2.48 mL (-0.97) per year

mean difference -0.71 mL (95% CI -2.56–1.15)

p = 0.40

Total participants: 120

Read by software from the paper's abstract

What was tested

Treatment tested

  • Lamotrigine

    Sodium channel alpha subunit blocker

What it measured

Main measures

  • Change in central brain volume on MRI using the 'Loseff method'

    MRI lesionsBrain volume loss

  • Based on the assumption that axonal loss is a key mechanism of progressive cerebral atrophy in MS, the primary outcome will be the rate of reduction of partial cerebral volume over two years. We have chosen a method that has very good reproducibility, is sensitive in detecting progressive cerebral atrophy in secondary progressive MS and has been used effectively in a previous multi−centre placebo

    MRI lesionsBrain volume loss

Other measures (9)

  • Change in whole brain volume on MRI using Brain Boundary Shift Integral

    MRI lesionsBrain volume loss

  • Number and volume of new T2 high intensity lesion volume on T2 weighted MRI

    MRI lesions

  • Number and volume of new T1 low signal lesion volume on T1 weighted MRI

    MRI lesions

  • Ratio of new T1 to new T2 lesions on MRI

    MRI lesions

  • Change in magnetisation transfer ratio in normal MRI normal appearing white matter and normal appearing grey matter.

    MRI lesionsMyelin repair

  • Change in upper cervical cord cross sectional area using the 'Loseff method' on MRI

    MRI lesions

  • Change in Kurtzke's Extended Disability Scaling Score.

  • Change in Multiple Sclerosis Functional Composite.

  • Change in Multiple Sclerosis Impact Scale.

Who could take part

Progressive MS · 18 to 60 · EDSS 4.0 to 6.5

Show the full criteria

Inclusion criteria

* Age 18 to 60 * Progression rather than clinical relapse is the major cause for increased disability over the preceding 2 years * EDSS 4.0-6.5

Exclusion criteria

* Very rapid deterioration in EDSS, >2 points over 6 months * Use of Mitoxantrone in the preceding year * Use of sodium channel blockers or calcium channel blockers in the preceding 2 weeks * Use of corticosteroids in preceding 2 months * Use of neuroprotective agents or immunosuppressants in the preceding 6 months * Evidence of significant hepatic or renal impairment either in clinical history or blood results. * Prior untoward reactions to lamotrigine, or severe temperature dependent symptoms * Contraindications to MRI

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

A present there is no safe treatment for reducing rate at which disability worsens in people with secondary progressive multiple sclerosis. Recent research has suggested the possibility that drugs that act by blocking the entry of sodium into nerve cells can protect nerve fibres in the brain and spinal cord. In this trial, the investigators will test whether one such drug, called lamotrigine, can prevent damage to nerve fibres and reduce the rate at which MS worsens. The period of treatment in the trial will run for 2 years.

Papers

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History

    1. Started

      Nov 2005

    2. Main results due

      Jan 2009

    3. Finished

      Feb 2009

    Assembled by software from public sources.