Intrathecal Methotrexate for Progressive Multiple Sclerosis: An Open Label Single Arm Study

• Status: Unknown status
• Trial end date: 2018-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tel-Aviv Sourasky Medical Center
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

• Age 18-75 years

• Clinically definite diagnosis of MS according to McDonald criteria 2010.

• Progressive disease form defined by confirmed expanded disability status scale (EDSS) progression without relapse by at least 0.5 point or greater in the six months prior to enrollment.

Exclusion Criteria:

• Pregnancy

• Active infection

• Significant associated medical condition such as malignancy, heart disease or concurrent other autoimmune condition.

• Known allergy to MTX.

• WBC<4000 cells/µL

• Lym<800 cells/µL

• Treated with fingolimod or natalizumab 3 months prior to enrollment