Clinical Trial: Intrathecal Rituximab in Progressive Multiple Sclerosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Intrathecal Rituximab in Progressive Multiple Sclerosis

Brief Summary: The goal of investigators is to study the kinetics of action of a single dose of intrathecally-infused rituximab upon cerebro-spinal fluid (CSF) biological targets in progressive MS patients. Various markers of central nervous system inflammation (osteopontin, Tumor Necrosis Factor α, IgG secretion) and neurodegeneration (neurofilament) are studied at multiple time-points, assuming that a definitive action upon CSF biological targets would be strongly predictive of a delayed clinical action.

Detailed Summary:

• Background : Multiple sclerosis (MS) is the most frequent inflammatory disorder leading to impairment in young people. Although many drugs are now available to treat the early relapsing-remitting phase of MS (RR-MS), impairment is mostly linked to the secondary progressive phase of MS. Since no treatment proved to efficiently prevent or cure this progressive phase, treating this phase remains challenging. In fact, progressive phase is associated with a fence-ringed intrathecal compartmentalization of inflammation, leading to the unavailability of most immunosuppressive drugs. As a consequence, investigators here propose to shift the therapeutic paradigm in MS to a new paradigm based on intrathecal infusion of monoclonal antibodies (mAb) aimed at eradicate intrathecal inflammation. Rituximab is a mAb targeting CD20+ B-lymphocytes. Positive results in RR-MS were obtained after blood infusion of rituximab, but results were negative in progressive MS, probably due to the very low penetration of the blood brain barrier. Since intrathecal rituximab is already used in central nervous system (CNS) lymphomas, investigators propose to use it this way in progressive MS.

• Detailed description : An optimal dosage of rituximab for intrathecal infusion was choose using data already obtained in CNS lymphoma, acknowledging that 20mg offers the higher dosage with good tolerance profile. In order to isolate rituximab effect, a control group is treated by steroids since steroids are required before rituximab infusion. Moreover, B-lymphocytes depletion in CSF will probably be transient, as it is when rituximab is infused in blood. Assuming that CSF B-cells repopulation may be facilitated by peripheral B-cells, a group was assigned to receive also blood infusion of rituximab. CSF will be examined at multiple time points to assess the time frame of biological effect obtained in C
Sponsor: Centre Hospitalier de PAU

Current Primary Outcome: Change in osteopontin level in CSF [ Time Frame: at day 4, day 21, day 180 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in Tumor Necrosis Factor alpha level in CSF [ Time Frame: day 4, day 21, day 180 ]
  • Change in IgG synthesis in CSF [ Time Frame: day 4, day 21, day 180 ]
  • Change in neurofilament level in CSF [ Time Frame: day 4, day 21, day 180 ]


Original Secondary Outcome: Same as current

Information By: Centre Hospitalier de PAU

Dates:
Date Received: September 7, 2015
Date Started: September 2015
Date Completion: September 2017
Last Updated: October 1, 2015
Last Verified: October 2015