- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00257855
A Randomised Controlled Trial of Neuroprotection With Lamotrigine in Secondary Progressive Multiple Sclerosis
A Randomised Controlled Trial of Neuroprotection With Lamotrigine in Secondary Progressive Multiple Sclerosis: Single Centre, Phase 2 Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Aims: To assess whether the sodium channel blocker lamotrigine has a neuroprotective, disease modifying effect on a) the rate of axonal degeneration and b) the accumulation of disability in patients with SPMS.
Methodology: We propose to recruit 120 people with SPMS in whom progression rather than relapse is the major cause of increasing disability into a double blind parallel group controlled trial lasting two years in which random allocation would be made to receive treatment with either lamotrigine or placebo. We anticipate that patient recruitment, follow-up and trial management could be achieved readily across four proposed sites in London. The primary endpoint would be an effect of treatment on cerebral atrophy, which correlates with other MR markers of axonal loss, and which can be measured reliably and sensitively using recently developed MR techniques. The trial is powered to detect a 60% beneficial effect on the rate of development of cerebral atrophy. Secondary endpoints would include effects of treatment on spinal cord atrophy and on clinical measurements of impairment/disability. MR measures of brain volume and cervical spinal cord cross-sectional area and scores of clinical impairment/disability would be determined at entry, and then after 12 and 24 months. Brain volume would be measured additionally at 6 and 18 months. Clinical follow-up would occur every 3 months, and interim analysis is planned at 12 months.
Utilization of results: A phase 2 trial of sodium channel blockade in SPMS is timely, given recent advances arising from experimental and imaging work. A successful outcome would enable sufficiently powered phase 3 trials to be implemented, but perhaps more significantly would demonstrate a novel, safe neuroprotective strategy to reduce long-term disability in this disorder.
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
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London, United Kingdom, WC1 3BG
- National Hospital For Neurology and Neurosurgery
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Change in central brain volume on MRI using the 'Loseff method'
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Secondary Outcome Measures
Outcome Measure |
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Change in whole brain volume on MRI using Brain Boundary Shift Integral
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Number and volume of new T2 high intensity lesion volume on T2 weighted MRI
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Number and volume of new T1 low signal lesion volume on T1 weighted MRI
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Ratio of new T1 to new T2 lesions on MRI
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Change in magnetisation transfer ratio in normal MRI normal appearing white matter and normal appearing grey matter.
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Change in upper cervical cord cross sectional area using the 'Loseff method' on MRI
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Change in Kurtzke's Extended Disability Scaling Score.
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Change in Multiple Sclerosis Functional Composite.
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Change in Multiple Sclerosis Impact Scale.
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Collaborators and Investigators
Investigators
- Study Director: Raju Kapoor, MD PhD, National Hospital For Neurology and Neurosurgery
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Neoplasms
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Neoplastic Processes
- Multiple Sclerosis
- Multiple Sclerosis, Chronic Progressive
- Sclerosis
- Neoplasm Metastasis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- Anticonvulsants
- Sodium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Lamotrigine
Other Study ID Numbers
- 2005-001949-42
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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