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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
michal roll, Tel-Aviv Sourasky Medical Center

Brief 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.


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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment
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.




Primary Outcome Measures :
  1. 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)

  2. 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.


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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Contact: Arnon Karni, MD 052-4266733 arnonk@tlvmc.gov.il
Contact: Oren Weintraub, MPHA 03-6915138 orenw@tlvmc.gov.il

Sponsors and Collaborators
Tel-Aviv Sourasky Medical Center
Publications:
Sadiq SA (2005) Multiple sclerosis. In: Rowland LP (ed) Merritt's neurology, 11th edn. Lippincott Williams and Wilkins, Philadelphia, pp 941-963

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Responsible Party: michal roll, Director R&D Division, Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier: NCT02644044    
Other Study ID Numbers: 0166-15-TLV
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: December 31, 2015
Last Verified: December 2015
Keywords provided by michal roll, Tel-Aviv Sourasky Medical Center:
Progressive multiple sclerosis
methotrexate
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors