Effect of Tysabri in Patients With Relapsing-Remitting Multiple Sclerosis: A Follow-up Magnetization Transfer Imaging (MTI) Study

This study has been completed.
Sponsor:
Collaborator:
Biogen Idec
Information provided by (Responsible Party):
Robert Zivadinov, MD, PhD, University at Buffalo
ClinicalTrials.gov Identifier:
NCT00937677
First received: July 9, 2009
Last updated: September 6, 2011
Last verified: September 2011
  Purpose

The primary objective of this study is to define the effect of Tysabri in patients with relapsing-remitting (RR) multiple sclerosis (MS) over 2 years. The investigators will also explore the extent of remyelination in MS patients treated with Tysabri over 2 years.

A secondary objective of this study is to investigate differences in the capacity for remyelination between patients who do or do not respond to Tysabri monotherapy during the same 24 months.

A tertiary objective of this study is to monitor Tysabri effect in MS antiphospholipid antibodies positive and MS antiphospholipid antibodies negative patients and to determine perfusion differences according to the antiphospholipid antibodies positivity status.


Condition Intervention
Multiple Sclerosis
Drug: Tysabri

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Effect of Natalizumab (Tysabri®) on Remyelination in Patients With Relapsing-remitting Multiple Sclerosis. A Follow-up Voxel-wise Magnetization Transfer Imaging Study.

Resource links provided by NLM:


Further study details as provided by University at Buffalo:

Primary Outcome Measures:
  • To define the effect of Tysabri monotherapy on a voxel-wise basis using magnetization transfer ratio dynamic mapping of the lesions and normal appearing brain tissue in patients with relapsing-remitting multiple sclerosis. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To investigate differences in the capacity for remyelination measured by MTR between patients who do or do not respond to Tysabri monotherapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 85
Study Start Date: November 2007
Study Completion Date: November 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
63 patients with relapsing-remitting Multiple Sclerosis who are enrolled in the TOUCH program and have been taking Tysabri monotherapy for 2 years.
Drug: Tysabri

Infusion of TYSABRI® 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP over approximately one hour at month 0 and 12 and 24 months. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP.

Use of filtration devices during administration has not been evaluated. Other medications should not be injected into infusion set side ports or mixed with TYSABRI®.

TYSABRI® concentrate is supplied as 300 mg natalizumab in a sterile, single-use vial free of preservatives. Each package contains a single-use vial.

Other Name: Natalizumab
2
22 age- and sex-matched normal controls who completed 1 year follow-up.

Detailed Description:

Magnetization transfer imaging (MTI) is a widely used tool for characterizing the evolution of multiple sclerosis (MS) lesions and normal appearing brain tissue (NABT). As remyelination and demyelination are heterogeneous in each lesion and NABT, techniques such as voxel-wise based MTR dynamic mapping may help predict an individual's clinical course, as well as the effect of treatment, by revealing evidence of myelin repair and neuroprotection.

Natalizumab (Tysabri) showed a robust effect on the decrease of inflammation in phase II and III clinical trials, as evidenced by the decrease in Gd enhancing and T2 lesions and on the decrease of clinical activity as measured by reduction of clinical relapses and progression of disability. The effect of Tysabri on non-conventional measures is only partially known.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

MS patients that are followed at the Jacobs Neurological Institute, University at Buffalo, Buffalo NY.

Criteria

Inclusion Criteria:

  • Patient diagnosed with clinically definite MS according to the Polman criteria
  • Age 18-65
  • Have a RR disease course
  • Have EDSS scores less than or equal to 5.5 {Kurtzke, 1983 #15}
  • Have disease duration less than 20 years
  • Fulfilled the TOUCH enrollment requirements and started on Tysabri monotherapy
  • Signed informed consent
  • None of the exclusion criteria

Exclusion Criteria:

  • Primary progressive, secondary progressive, or progressive relapsing MS. Primary progressive, secondary progressive or progressive relapsing multiple sclerosis.
  • A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to drug start.
  • History of, or abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, and/or other major disease that, in the opinion of the investigator, would preclude the administration of natalizumab for the duration of the study.
  • History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
  • Abnormal blood tests, performed at the screening visit, which exceed any of the limits defined below:
  • ALT/ SGPT, or AST/ SGOT > three times the upper limit of normal (i.e., 3xULN).
  • Total white blood cell (WBC) count <2,300/mm3.
  • Platelet count <100,000/mm3.
  • Creatinine > 2xULN.
  • Prothrombin time (PT) > ULN.
  • Any prior treatment during the 2 weeks prior to study screening with agents such as IFN-β, GA, IVIG, or on the following immunosuppressant therapies for less than 3 months: mitoxantrone, cyclophosphamide, cladribine, fludarabine, cyclosporine, azathioprine, methotrexate, Cellcept, etc.
  • History of alcohol or drug abuse within 2 years prior to randomization.
  • Female subjects who are not postmenopausal for at least 1 year, surgically sterile, or willing to practice effective contraception (as defined by the investigator) during the study. The rhythm method is not to be used as the sole method of contraception.
  • Nursing mothers, pregnant women, and women planning to become pregnant while on study.
  • Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
  • Any other reasons that, in the opinion of the Investigator, indicate that the subject is unsuitable for enrollment into this study.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00937677

Locations
United States, New York
Jacobs Neurological Institute
Buffalo, New York, United States, 14203
Sponsors and Collaborators
University at Buffalo
Biogen Idec
Investigators
Principal Investigator: Robert Zivadinov, MD, PHd University at Buffalo
  More Information

No publications provided by University at Buffalo

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert Zivadinov, MD, PhD, Professor of Neurology, University at Buffalo
ClinicalTrials.gov Identifier: NCT00937677     History of Changes
Other Study ID Numbers: BNAC/Tysabri/01
Study First Received: July 9, 2009
Last Updated: September 6, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University at Buffalo:
Tysabri
VWMTR

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 22, 2014