Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

Not Applicable

Completed

Conditions: Multiple Sclerosis

Interventions: Drug: Tysabri

Registration Number: NCT01071512

Lead Sponsor: University of Chicago

Brief Summary: The long-term objective is to further establish the role of Tysabri in preventing neurological degeneration in multiple sclerosis (MS) and to establish powerful and efficient new markers for neurological degeneration in MS. The study intends to correlate cognition with two instruments and their measurements-MRI and OCT (optical coherence tomography).

Detailed Description: The specific aims are:

1. To determine the effects of Tysabri on cognition (memory, thought processes, etc.)

2. To determine the effects of Tysabri on specific MRI markers for cognitive dysfunction

3. To determine the effects of Tysabri on retinal nerve fiber layer thickness (RNFL) using optical coherence tomography (OCT), a special instrument used in ophthalmology

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

18 through 60 years of age inclusive
Diagnosis of relapsing remitting multiple sclerosis
Prior to treatment phase, have had disease activity with at least 1 documented relapse during the previous year OR 2 documented relapses during the previous 2 years OR one or more new MRI lesions (Gd+ and/or T2 hyperintense)
An Expanded Disability Status Scale (EDSS) score of 0-4.5 inclusive
Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to treatment
Never been treated with Tysabri/natalizumab.

Exclusion Criteria

Another type of MS other than relapsing remitting multiple sclerosis (RRMS)
A history of chronic disease of the immune system other than MS or a known immunodeficiency syndrome/immunocompromised
A history or presence of cancer (except for successfully treated basal or squamous cell carcinoma of skin)
Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively
Have received any live or live attenuated vaccines (including for varicella-zoster virus or Measles) within the last 2 months
Have received total lymphoid irradiation or bone marrow transplantation
Have been treated with: corticosteroids or adrenocorticotropic hormones (ACTH) within the last month, IFN-β or glatiramer acetate within the last 3 months, immunosuppressive medications such as azathioprine or methotrexate within the last 6 months, immunoglobulins and/or monoclonal antibodies (including natalizumab) within the last 6 months, or cladribine, cyclophosphamide or mitoxantrone at any time.
Any medically unstable condition or a progressive neurological disorder, other than MS, which may affect participation in the study
History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal or other major disease
Unable to undergo MRI scans, including claustrophobia, have a pacemaker or history of hypersensitivity to gadolinium-DTPA
Have had a relapse within 30 days prior AND/OR not stabilized from a previous relapse
History of severe allergic or anaphylactic reactions or known drug hypersensitivity to natalizumab/Tysabri
A clinically significant infectious disease, such as cellulitis, pneumonia, septicemia
History of progressive multifocal leukoencephalopathy(PML)
Participation in any clinical research study evaluating another investigational drug or therapy within the last 6 months
History of Tysabri therapy
Abnormal screening blood test
Females who are not postmenopausal for at least 1 year, surgically sterile or willing to practice effective contraception during the study
Nursing mothers, pregnant women, and women planning to become pregnant while on study

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tysabri	Tysabri	Natalizumab 300 mg IV every 4 weeks

Primary Outcome Measures

Name	Time	Method
Change in Cognitive Function Over Time	Baseline, 48 weeks, 96 weeks	Cognitive function was assessed using the oral version of the Symbol Digit Modalities Test (SDMT). The number of correct responses in 90 seconds was recorded (possible range 0-110). For analysis, SDMT scores were converted to z-scores using published age and education based norms. A negative z-score indicates a SDMT score below the mean based on the age and education based norms, for example a z-score of -2 = 2 standard deviations below the mean; a positive z-score indicating a score above the mean. Higher scores indicate better cognitive function.

Secondary Outcome Measures

Name	Time	Method
Change Over Time in Retinal Nerve Fiber Layer Thickness	Baseline, 24, 48, 72, and 96 weeks	Retinal Nerve Fiber Layer (RNFL) thickness was measured using spectral domain OCT scans by a trained technician. Scans were performed without pupil dilation.
Change Over Time in Normalized Thalamic Volume	Baseline, 48 weeks, 96 weeks	Measured on MRI scan
Change Over Time in Normalized Hippocampal Volume	Baseline, 48 weeks, 96 weeks	Measured on MRI scan
Change Over Time in Brain Parenchymal Fraction	Baseline, 48 weeks, 96 weeks	Measured based on MRI scan on a 3T Phillips scanner. This is a measure of brain atrophy (i.e., brain volume loss) with lower values indicating greater atrophy (possible range 0-1).