Intrathecal Methotrexate for Progressive Multiple Sclerosis: An Open Label Single Arm Study
Status:
Unknown status
Trial end date:
2018-01-01
Target enrollment:
Participant gender:
Summary
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.