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.

Inclusion Criteria:

• A diagnosis of definite multiple sclerosis

• Treatment with DMDs for at least 6 months prior to baseline visit*

• CSF NFL level ≥ 0.380ng/mL

• EDSS score between 3.5 and 6.0

• No history of relapses in the 6 months prior to the baseline visit

• A history of slow progression of disability, objective or subjective, over a period of at least 6 months prior to baseline

• Age 18-60 years

  • [Temporary interruption is permitted at the discretion of the investigator for a period of up to 8 weeks to prevent inflammatory MS reactivation. The cases where this could happen include for example switching DMDs that require a washout period as per clinical practice. When there are safety concerns, as in Lymphopenia or other side effects induced by the DMD, the interruption period can exceed 8 weeks as per clinical need. If reactivation of MS occurs with a relapse the investigator will assess if this meets withdrawal criteria 6.]

Exclusion Criteria:

• Pregnant or breastfeeding or unwilling to use adequate contraception.*

• Participants with a diagnosis of primary progressive PP MS or primary relapsing PR MS.

• A clinical relapse or pulsed intravenous or oral steroids in the 6 months preceding the baseline assessment.

• Participants presenting with medical disorder deemed severe or unstable by the CI such as poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (>2.5 times ULN) and abnormal complete blood count (in particular leukopenia, as defined by a lymphocyte count <500, neutrophil count <1.5 or platelet count <100, or thrombocytopenia <1.5 LLN), or any medical condition which, in the opinion of the investigator, would pose additional risk to the participant.

• Infection with hepatitis B or hepatitis C or human immunodeficiency virus.

• Exposure to any other investigational drug within 30 days of enrolment in the study.

• Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (CSSRS).

• Prior history of malignancy unless an exception is granted by the Investigator.

• History of uncontrolled drug or alcohol abuse within 6 months prior to screening.

• Past untoward reactions to OxCbz or Cbz

• Participants receiving OxCbz or Cbz in the previous 12 weeks from baseline

  • [Adequate methods of contraception are non hormonal methods such as barrier methods, intrauterine devices, surgical sterilisation (undergone by the participant or their partner). Female participants using hormonal only forms of contraception will be required to use an additional barrier method. True abstinence can be considered an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception. Non sexually active participants or those in same sex relationships will not be required to commence contraception.]