Intrathecal Methotrexate for Progressive Multiple Sclerosis: An Open Label Single Arm Study (ITMTXPMS)
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|ClinicalTrials.gov Identifier: NCT02644044|
Recruitment Status : Unknown
Verified December 2015 by michal roll, Tel-Aviv Sourasky Medical Center.
Recruitment status was: Not yet recruiting
First Posted : December 31, 2015
Last Update Posted : December 31, 2015
Multiple sclerosis (MS) is characterized pathologically by demyelination, axonal loss, and glial scar formation. Clinically, most patients have a relapsing-remitting course of MS (RRMS) that over time may become progressive without remissions - a secondary progressive MS (SPMS). About 15% of patients have a progressive course from onset which is called primary progressive (PP).
Currently, there is no approved treatment for PPMS and for SPMS only therapy with mitoxantrone showed mild effect. Thus, more effective therapies need to be developed for treatment of SPMS and PPMS.
Methotrexate (MTX), an anti-metabolite, has been in clinical use since 1948 when it was found to produce temporary remission of acute childhood leukemia.
There are accumulating evidences that in progressive MS patients there are follicular lymphoid structures in the meninges and in the Virchow-Robin spaces. Therefore, intrathecal therapy may target the pathological follicular lymphoid activity.
The safety of intrathecal MTX (ITMTX) has been demonstrated by its widespread use in treating lymphoproliferative diseases and leptomeningeal metastases. Sadik et. Al. reported about the feasibility and safety of using intrathecal methotrexate (ITMTX) as a treatment for unresponsive patients with progressive forms of MS. In their open label study they found that ITMTX may have a beneficial effect in progressive forms of MS and that it was well tolerated with no serious adverse events.
The investigators aim is to evaluate the efficacy , safety and tolerability of intrathecal methotrexate administration every 3 months in progressive 30 patients with progressive MS. The investigators will evaluate clinical, laboratory evaluation of the blood and cerebrospinal fluid as well as the MRI scans of the participants. Each patient will be treated 4 times for 1 year with the option to continue for another 1 more year with the same protocol.
|Condition or disease||Intervention/treatment||Phase|
|To Evaluate the Effect of Therapy With IT MTX on the Disease Course of Patients With Progressive MS||Drug: Intrathecal methotrexate||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Intrathecal Methotrexate for Progressive Multiple Sclerosis: An Open Label Single Arm Study|
|Study Start Date :||January 2016|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||January 2018|
Treatment with IT methotrexate
Drug: Intrathecal methotrexate
12.5 mg of methotrexate diluted to a concentration of up to 4 mg/mL in 0.9 percent sodium chloride with 4 mg Dexamethasone via lumbar puncture needle.
- The change in disability ( Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 1 year ]Disability will be measured every visit by the Multiple Sclerosis Functional Composite (MSFC)
- Safety and tolerability (adverse events) [ Time Frame: each adverse event will be followed up until resolution ]adverse events will be followed until resolution. Serious adverse events will be reported to the IRB within 24 hours of noticed.
- Changes in brain MRI measurements [ Time Frame: 1 year ](Composite measure) We will measure new gd+ enhancing lesions, number of lesions, brain and upper spinal cord atrophy and cortical thickness and compare these measure between the time before and after treatment along. Overall each participant will undergo 5 scans , the first before treatment installation and then before each treatment . one scan will be done 3 month after the last treatment
- Laboratory measurements [ Time Frame: 1 year ](Composite measure) Cerebrospinal fluid (CSF) sample will be obtained and analyze for parameters including cell count and differential, protein and glucose concentration, oligoclonal bands, IgG concentration, cellular analysis by flow cytometry for CD3+, CD20+, CD14+ cell subsets, and measurement of several soluble mediators such as: CXCL13, CD23, light chains, TNFa, IFNg, IL-17, IL-2, IL-10, BDNF and Neurofilaments will be studied by ELISA
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): NCT02644044
|Contact: Arnon Karni, MDfirstname.lastname@example.org|
|Contact: Oren Weintraub, MPHAemail@example.com|