People with multiple sclerosis (MS) have nerve loss even without acute inflammatory relapses, as obvious in the progressive phase of disease. Drugs that may prevent nerve loss work better in earlier stages when it is difficult to measure progressive disability. But it is now possible to measure the nerve loss as neurofilament light (NFL) in the cerebrospinal fluid (CSF). This is a trial of a neuroprotective drug, oxcarbazepine, which showed benefit in an animal model of multiple sclerosis. The investigators will use an innovative outcome, a reduction in the content of NFL in the CSF, as well as the usual clinical disability and imaging methods, to measure the success of the oxcarbazepine as a neuroprotective agent in MS. The use of NFL, a surrogate marker of neurodegeneration, allows a blinded and accurate outcome.
Patients who have been identified as potentially eligible for this trial and referred to us will be invited to take part in the study and provided with information given as a patient information sheet. This includes patients with clinical definite MS who are on any DMDs, have not had a MS relapses for at least 6 months and feel (subjective) or are observed (objective) to have progressing disability. For screening patients will sign the informed consent form after discussion and make sure they fulfil inclusion and exclusion criteria, they will have a neurological and a brief suicidality assessment and will have safety blood and urine tests. Patients will have a lumbar puncture to measure NFL in CSF. If it is above the threshold, showing that there is ongoing damage to the myelin, we will invite them to continue in the trial. Patients will have a baseline brain and spinal cord MRI and OCT, clinical/neurological examination and will have a repeat lumbar puncture and collection of blood, urine and saliva. Patients will be blindly randomised to oxcarbazepine vs placebo and given the bottles of medication with each participant's individualised label. At two and four weeks after the baseline visit, patients will have a phone visit when investigators will collect details of new symptoms, new medication and generally advise participants. The tablets should have been increases to two tablets in the morning and two tablets in the evening. Patients will be seen by the study team at 13 weeks after initiation of the drug and again at 25 and 37 weeks when they will have an OCT, lumbar puncture, collection of blood, urine and saliva after general, visual, neurological and cognitive assessments/questionnaires. The final visit will be at week 48, when a final lumbar puncture, preceded by clinical measures including general, visual, neurological and cognitive assessments/questionnaires, MRI , OCT and blood, urine \& saliva collection. The measurement of NFL will be repeated from the CSF samples on the same at the end of the study to determine whether patients with MS who were on oxcarbazepine had a reduction in the levels of CSF NFL.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
Oxcarbazepine 150mg tablet, over encapsulated and back-filled with Microcrystalline Cellulose/Magnesium Stearate 1%.
Placebo in a matched capsule containing Microcrystalline Cellulose/Magnesium Stearate 1%.
Barts Health NHS Trust
London, United Kingdom
Relative reduction of CSF neurofilament light chain levels
CSF obtained from lumbar punctures will be used to determine neurofilament light chain levels from baseline to 48 weeks between the active and placebo treated arms.
Time frame: From baseline to week 48
Safety of Oxcarbazepine in multiple sclerosis patients
Safety of OxCbz in multiple sclerosis patients as indicated by a comparison of adverse events to expected side effects outlined in the summary of product characteristics
Time frame: Ongoing throughout the trial
Relative reduction of CSF neurofilament levels
CSF obtained from lumbar punctures will be used to determine neurofilament light chain levels from baseline to 24 weeks and from 24 to 48 weeks between the active and placebo treated arms.
Time frame: baseline, 24 weeks and 48 weeks
Change in clinical outcome measured by neurological examination.
A neurological examination, including EDSS and Sloan chart will be performed by a study neurologist.
Time frame: Baseline, week 24 and week 48
Change in clinical outcome measured by cognitive assessment
Cognitive assessment will consist of Symbol Digit Modalities Test (SDMT).
Time frame: Baseline, week 12, 24, 36 and 48
Change in patient reported outcomes measured by questionnaires
Patient questionnaires will include SF36, MSWS, MSIS-29 v2, Patient Pain Assessment and Patient Fatigue Assessment
Time frame: Baseline, weeks 12, 24, 36 and 48
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