Protective Role of Oxcarbazepine in Multiple Sclerosis

• Status: Completed
• Trial end date: 2018-01-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen Mary University of London
• Collaborators: Barnet and Chase Farm Hospitals NHS Trust; Barts & The London NHS Trust; Basildon and Thurrock University Hospitals NHS Foundation Trust; Mid and South Essex NHS Foundation Trust; National Multiple Sclerosis Society; Novartis Pharmaceuticals; Royal Free Hospital NHS Foundation Trust; Southend University Hospital; St George's Healthcare NHS Trust; University College, London
• Treatments: Carbamazepine; Neuroprotective Agents; Oxcarbazepine

Criteria

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.]