Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Tysabri

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tysabri; Natalizumab 300 mg IV every 4 weeks	Drug: Tysabri; Infuse TYSABRI® 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP over approximately one hour. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP. Tysabri will be infused every four weeks.; Other Names: Natalizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive Function Over Time	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.	Baseline, 48 weeks, 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Over Time in Retinal Nerve Fiber Layer Thickness	Retinal Nerve Fiber Layer (RNFL) thickness was measured using spectral domain OCT scans by a trained technician. Scans were performed without pupil dilation.	Baseline, 24, 48, 72, and 96 weeks
Change Over Time in Brain Parenchymal Fraction	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).	Baseline, 48 weeks, 96 weeks
Change Over Time in Normalized Thalamic Volume	Measured on MRI scan	Baseline, 48 weeks, 96 weeks
Change Over Time in Normalized Hippocampal Volume	Measured on MRI scan	Baseline, 48 weeks, 96 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Biogen
• Investigators: Principal Investigator: Jacqueline Bernard, M.D., University of Chicago

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 17, 2010
• First Submitted That Met QC Criteria: February 18, 2010
• First Posted (Estimate): February 19, 2010

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: September 22, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: MRI; Multiple Sclerosis; OCT; cognition; Tysabri
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Nerve Degeneration; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: 10-094A