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Multiple SclerosisPhase 2PROXIMUSNCT02104661

Protective Role of Oxcarbazepine in Multiple Sclerosis

A Phase 2 study testing Oxcarbazepine in people with Multiple Sclerosis, run by Queen Mary University of London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Oxcarbazepine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteUnited Kingdom
Study dates
Oct 2014to 31 Jan 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.]

Who cannot join

  • 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.
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  • 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.]

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Barts Health NHS Trust

    London, E1 1BB

Other trials in United Kingdom

About this study

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

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.

Read the 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 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.

Being tested
Oxcarbazepine, Placebo
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OxcarbazepineDrug

    Also called Trileptal

    Oxcarbazepine 150mg tablet, over encapsulated and back-filled with Microcrystalline Cellulose/Magnesium Stearate 1%.

  • PlaceboDrug

    Placebo in a matched capsule containing Microcrystalline Cellulose/Magnesium Stearate 1%.

Study groups in NCT02104661
Study groupRoleWhat they receive
OxCarbazepine TreatmentExperimentalTreated for 48 weeks with OxCarbazepine 150mg twice a day alongside current DMDs.
Receives: Drug: Oxcarbazepine
OxCarbazepine PlaceboPlacebo comparatorTreated for 48 weeks with matched placebo 1 tablet twice a day alongside current DMDs
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From baseline to week 48

Secondary outcomes (5)
  1. 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

    Measured: Ongoing throughout the trial

  2. 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.

    Measured: baseline, 24 weeks and 48 weeks

  3. Change in clinical outcome measured by neurological examination.

    A neurological examination, including EDSS and Sloan chart will be performed by a study neurologist.

    Measured: Baseline, week 24 and week 48

  4. Change in clinical outcome measured by cognitive assessment

    Cognitive assessment will consist of Symbol Digit Modalities Test (SDMT).

    Measured: Baseline, week 12, 24, 36 and 48

  5. Change in patient reported outcomes measured by questionnaires

    Patient questionnaires will include SF36, MSWS, MSIS-29 v2, Patient Pain Assessment and Patient Fatigue Assessment

    Measured: Baseline, weeks 12, 24, 36 and 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2014 (estimated)
  2. Study startOct 2014
  3. Primary completion31 Jan 2018
  4. Study completion31 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02104661
Sponsor's protocol ID
8722
Other IDs
2013-002419-87, 14-LO-0185
Acronym
PROXIMUS
Status last verified
Apr 2018
First submitted
1 Apr 2014
Last updated
18 Apr 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29;338(5):278-85. doi: 10.1056/NEJM199801293380502.

    PubMed 9445407
  • Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010 Jul;133(Pt 7):1900-13. doi: 10.1093/brain/awq076. Epub 2010 Apr 27.

    PubMed 20423930
  • Petzold A, de Boer JF, Schippling S, Vermersch P, Kardon R, Green A, Calabresi PA, Polman C. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2010 Sep;9(9):921-32. doi: 10.1016/S1474-4422(10)70168-X.

    PubMed 20723847
  • Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. doi: 10.1007/s00415-005-0934-5. Epub 2005 Jul 27.

    PubMed 16044212
  • Franklin RJ, Ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008 Nov;9(11):839-55. doi: 10.1038/nrn2480.

    PubMed 18931697
  • Stys PK. General mechanisms of axonal damage and its prevention. J Neurol Sci. 2005 Jun 15;233(1-2):3-13. doi: 10.1016/j.jns.2005.03.031.

    PubMed 15899499
  • Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009 May;5(5):256-66. doi: 10.1038/nrneurol.2009.41.

    PubMed 19488083
  • Altmann DR, Jasperse B, Barkhof F, Beckmann K, Filippi M, Kappos LD, Molyneux P, Polman CH, Pozzilli C, Thompson AJ, Wagner K, Yousry TA, Miller DH. Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis. Neurology. 2009 Feb 17;72(7):595-601. doi: 10.1212/01.wnl.0000335765.55346.fc. Epub 2008 Nov 12.

    PubMed 19005170
  • Kapoor R, Furby J, Hayton T, Smith KJ, Altmann DR, Brenner R, Chataway J, Hughes RA, Miller DH. Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Neurol. 2010 Jul;9(7):681-8. doi: 10.1016/S1474-4422(10)70131-9. Epub 2010 Jun 8.

    PubMed 20621711
  • Ebers GC, Heigenhauser L, Daumer M, Lederer C, Noseworthy JH. Disability as an outcome in MS clinical trials. Neurology. 2008 Aug 26;71(9):624-31. doi: 10.1212/01.wnl.0000313034.46883.16. Epub 2008 May 14.

    PubMed 18480462
  • Lycke JN, Karlsson JE, Andersen O, Rosengren LE. Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):402-4. doi: 10.1136/jnnp.64.3.402.

    PubMed 9527161
  • Malmestrom C, Haghighi S, Rosengren L, Andersen O, Lycke J. Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS. Neurology. 2003 Dec 23;61(12):1720-5. doi: 10.1212/01.wnl.0000098880.19793.b6.

    PubMed 14694036
  • Salzer J, Svenningsson A, Sundstrom P. Neurofilament light as a prognostic marker in multiple sclerosis. Mult Scler. 2010 Mar;16(3):287-92. doi: 10.1177/1352458509359725. Epub 2010 Jan 19.

    PubMed 20086018
  • Petzold A, Eikelenboom MJ, Keir G, Grant D, Lazeron RH, Polman CH, Uitdehaag BM, Thompson EJ, Giovannoni G. Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study. J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):206-11. doi: 10.1136/jnnp.2004.043315.

    PubMed 15654034
  • Semra YK, Seidi OA, Sharief MK. Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability. J Neuroimmunol. 2002 Jan;122(1-2):132-9. doi: 10.1016/s0165-5728(01)00455-6.

    PubMed 11777552

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oxcarbazepine in people with Multiple Sclerosis, run by Queen Mary University of London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relative reduction of CSF neurofilament light chain levels (time frame: From baseline to week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02104661, which also lists 53 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2018.

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