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

NCT00937677 | Completed

• 1 other identifier: BNAC/Tysabri/01
• Study Type: observational
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis

Keywords

Tysabri; VWMTR

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (1)

• To investigate differences in the capacity for remyelination measured by MTR between patients who do or do not respond to Tysabri monotherapy.

  2 years

Study Arms (2)

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

2

22 age- and sex-matched normal controls who completed 1 year follow-up.

Interventions

Tysabri DRUG

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.

Also known as: Natalizumab

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University at Buffalo: lead
• Biogen: collaborator

Study Sites (1)

Jacobs Neurological Institute

Buffalo, New York, 14203, United States

Location

Related Publications (1)

• Zivadinov R, Dwyer MG, Hussein S, Carl E, Kennedy C, Andrews M, Hojnacki D, Heininen-Brown M, Willis L, Cherneva M, Bergsland N, Weinstock-Guttman B. Voxel-wise magnetization transfer imaging study of effects of natalizumab and IFNbeta-1a in multiple sclerosis. Mult Scler. 2012 Aug;18(8):1125-34. doi: 10.1177/1352458511433304. Epub 2011 Dec 22.

  PMID: 22194217 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Robert Zivadinov, MD, PHd

  University at Buffalo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 13, 2009
• Study Start: November 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: November 1, 2010
• Last Updated: September 7, 2011

Record last verified: 2011-09

Locations

US (1)