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Protective Role of Oxcarbazepine in Multiple Sclerosis

Information source: Queen Mary University of London
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Multiple Sclerosis

Intervention: Oxcarbazepine (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Queen Mary University of London

Official(s) and/or principal investigator(s):
Gavin Givannoni, Principal Investigator, Affiliation: Queen Mary University of London
Monica Calado Marta, Principal Investigator, Affiliation: Barts & The London NHS Trust

Overall contact:
Monica Calado Marta, Email: m.calado-marta@qmul.ac.uk

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.

Clinical Details

Official title: OxCarbazepine as a Neuroprotective Agent in MS: A Phase 2a Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Relative reduction of CSF neurofilament light chain levels

Secondary outcome:

Safety of Oxcarbazepine in multiple sclerosis patients

Relative reduction of CSF neurofilament levels

Change in clinical outcome measured by neurological examination.

Change in clinical outcome measured by cognitive assessment

Change in patient reported outcomes measured by questionnaires

Detailed description: 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 12 weeks after initiation of the drug and again at 24 and 36 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.

Eligibility

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- A diagnosis of definite multiple sclerosis

- Treatment with DMDs for at least 6 months

- EDSS score between 3. 5 and 6. 0

- No history of relapses in the preceding 6 months

- A history of slow progression of disability, objective or subjective, over a period

of at least 6 months

- Age 18-60 years

Exclusion Criteria:

- Pregnant or breastfeeding or unwilling to use adequate contraception.

- Participants who do not take a DMDs for 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 chief investigator, would pose additional risk to the participant.

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

- Participants receiving other sodium or calcium channel blockers in the previous 12

weeks

- 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 Chief Investigator.

- History of uncontrolled drug or alcohol abuse within 6 months prior to enrolment into

the study.

- Past untoward reactions to OxCbz or Cbz

Locations and Contacts

Monica Calado Marta, Email: m.calado-marta@qmul.ac.uk

Barts Health NHS Trust, London E1 1BB, United Kingdom; Recruiting
Monica Calado Marta, Email: m.calado-marta@qmul.ac.uk
Paul Foster Cofie, Phone: 0207 882 7150, Email: PaulFoster.Cofie@bartshealth.nhs.uk
Gavin Giovannoni, Principal Investigator
Monica Calado Marta, Principal Investigator
Olga Ciccarelli, Sub-Investigator
Jeremy Chataway, Sub-Investigator
Klaus Schmierer, Sub-Investigator
Raj Kapoor, Sub-Investigator
Anna Bellin, Sub-Investigator
Additional Information

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Starting date: October 2014
Last updated: August 21, 2015

Page last updated: August 23, 2015

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