Clinical trial NCT01071512: Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis
Official title: Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: MRI
OCT
Tysabri
Multiple Sclerosis
cognition
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2010-02-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in Cognitive Function Over Time
timeFrame: Baseline, 48 weeks, 96 weeks
Secondary outcomes:
measure: Change Over Time in Retinal Nerve Fiber Layer Thickness
timeFrame: Baseline, 24, 48, 72, and 96 weeks
measure: Change Over Time in Brain Parenchymal Fraction
timeFrame: Baseline, 48 weeks, 96 weeks
measure: Change Over Time in Normalized Thalamic Volume
timeFrame: Baseline, 48 weeks, 96 weeks
measure: Change Over Time in Normalized Hippocampal Volume
timeFrame: Baseline, 48 weeks, 96 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Jacqueline Bernard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: