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Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tysabri
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring MRI, OCT, Tysabri, Multiple Sclerosis, cognition

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tysabri

Arm Description

Natalizumab 300 mg IV every 4 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
Change Over Time in Normalized Thalamic Volume
Measured on MRI scan
Change Over Time in Normalized Hippocampal Volume
Measured on MRI scan

Full Information

First Posted
February 17, 2010
Last Updated
September 22, 2017
Sponsor
University of Chicago
Collaborators
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01071512
Brief Title
Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis
Official Title
Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
Biogen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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: To determine the effects of Tysabri on cognition (memory, thought processes, etc.) To determine the effects of Tysabri on specific MRI markers for cognitive dysfunction To determine the effects of Tysabri on retinal nerve fiber layer thickness (RNFL) using optical coherence tomography (OCT), a special instrument used in ophthalmology

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
MRI, OCT, Tysabri, Multiple Sclerosis, cognition

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tysabri
Arm Type
Experimental
Arm Description
Natalizumab 300 mg IV every 4 weeks
Intervention Type
Drug
Intervention Name(s)
Tysabri
Other Intervention Name(s)
Natalizumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Cognitive Function Over Time
Description
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.
Time Frame
Baseline, 48 weeks, 96 weeks
Secondary Outcome Measure Information:
Title
Change Over Time in Retinal Nerve Fiber Layer Thickness
Description
Retinal Nerve Fiber Layer (RNFL) thickness was measured using spectral domain OCT scans by a trained technician. Scans were performed without pupil dilation.
Time Frame
Baseline, 24, 48, 72, and 96 weeks
Title
Change Over Time in Brain Parenchymal Fraction
Description
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).
Time Frame
Baseline, 48 weeks, 96 weeks
Title
Change Over Time in Normalized Thalamic Volume
Description
Measured on MRI scan
Time Frame
Baseline, 48 weeks, 96 weeks
Title
Change Over Time in Normalized Hippocampal Volume
Description
Measured on MRI scan
Time Frame
Baseline, 48 weeks, 96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacqueline Bernard, M.D.
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

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Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

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