Protective Role of Oxcarbazepine in Multiple Sclerosis (PROXIMUS)
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|ClinicalTrials.gov Identifier: NCT02104661|
Recruitment Status : Recruiting
First Posted : April 4, 2014
Last Update Posted : January 10, 2017
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Drug: Oxcarbazepine Drug: Placebo||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||OxCarbazepine as a Neuroprotective Agent in MS: A Phase 2a Trial|
|Study Start Date :||October 2014|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||March 2018|
Experimental: OxCarbazepine Treatment
Treated for 48 weeks with OxCarbazepine 150mg twice a day alongside current DMDs.
Oxcarbazepine 150mg tablet, over encapsulated and back-filled with Microcrystalline Cellulose/Magnesium Stearate 1%.
Other Name: Trileptal
Placebo Comparator: OxCarbazepine Placebo
Treated for 48 weeks with matched placebo 1 tablet twice a day alongside current DMDs
Placebo in a matched capsule containing Microcrystalline Cellulose/Magnesium Stearate 1%.
- Relative reduction of CSF neurofilament light chain levels [ Time Frame: From baseline to week 48 ]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.
- Safety of Oxcarbazepine in multiple sclerosis patients [ Time Frame: Ongoing throughout the trial ]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
- Relative reduction of CSF neurofilament levels [ Time Frame: baseline, 24 weeks and 48 weeks ]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.
- Change in clinical outcome measured by neurological examination. [ Time Frame: Baseline, week 24 and week 48 ]A neurological examination, including EDSS and Sloan chart will be performed by a study neurologist.
- Change in clinical outcome measured by cognitive assessment [ Time Frame: Baseline, week 12, 24, 36 and 48 ]Cognitive assessment will consist of Symbol Digit Modalities Test (SDMT).
- Change in patient reported outcomes measured by questionnaires [ Time Frame: Baseline, weeks 12, 24, 36 and 48 ]Patient questionnaires will include SF36, MSWS, MSIS-29 v2, Patient Pain Assessment and Patient Fatigue Assessment
- MRI scan to measure neurodegeneration [ Time Frame: Baseline and week 48 ]MRI scan will measure brain grey matter atrophy, spinal cord atrophy and three novel measures, that have potential to detect more specific neuroaxonal abnormalities and the effect on them of a sodium blocking channel agent, such as OxCbz: (i) total sodium concentration, (ii) axonal diameter and (iii) axonal density.
- OCT to measure retinal nerve fibre layer (RNFL) for neurodegeneration [ Time Frame: Baseline and weeks 24 and 48 ]retinal nerve fibre layer (RNFL) constitutes a good surrogate marker of neurodegeneration of the unmyelinated axons in the optic nerve after optic neuritis it has also been demonstrated that RNFL thinning occurs in SPMS not previously affected by optic neuritis.
- Biological samples collected to test for biomarkers of MS and correlation with response to OxCbz as a neuroprotector [ Time Frame: Baseline, week 12, 24, 36 and 48 ]These biomarkers of MS include immunological, viral, CNS components of cellular and genetic markers in CSF/serum/urine samples. We will use these to compare between people who are treated/respond to treatment with OxCbz
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02104661
|Contact: Monica Calado Martaemail@example.com|
|Barts Health NHS Trust||Recruiting|
|London, United Kingdom, E1 1BB|
|Contact: Monica Calado Marta firstname.lastname@example.org|
|Contact: Omeada Adams 0207 882 7150 email@example.com|
|Principal Investigator: Gavin Giovannoni|
|Principal Investigator: Monica Calado Marta|
|Sub-Investigator: Olga Ciccarelli|
|Sub-Investigator: Jeremy Chataway|
|Sub-Investigator: Klaus Schmierer|
|Sub-Investigator: Raj Kapoor|
|Principal Investigator:||Gavin Givannoni||Queen Mary University of London|
|Principal Investigator:||Monica Calado Marta||Barts & The London NHS Trust|