Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

A study testing Tysabri in people with Multiple Sclerosis, run by University of Chicago at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Multiple Sclerosis
What is being tested?: Tysabri
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited States
Study dates: Apr 2010to Jan 2016
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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

Show all 19Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Chicago
Chicago, Illinois, 60637

Other trials in United States

About this study

Read the 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

Conditions: Multiple Sclerosis
Being tested: Tysabri
Keywords: MRI, OCT, Tysabri, Multiple Sclerosis, cognition
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TysabriDrug
Also called Natalizumab
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.

Study groups in NCT01071512
Study group	Role	What they receive
Tysabri	Experimental	Natalizumab 300 mg IV every 4 weeks Receives: Drug: Tysabri

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, 48 weeks, 96 weeks

Secondary outcomes (4)

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.
Measured: 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).
Measured: Baseline, 48 weeks, 96 weeks
Change Over Time in Normalized Thalamic Volume
Measured on MRI scan
Measured: Baseline, 48 weeks, 96 weeks
Change Over Time in Normalized Hippocampal Volume
Measured on MRI scan
Measured: Baseline, 48 weeks, 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2010Jan 2016

First posted19 Feb 2010 (estimated)
Study startApr 2010
Primary completionJan 2016
Study completionJan 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Multiple SclerosisStudies of the same condition, open and under way.
More trials run by University of ChicagoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01071512
Sponsor's protocol ID: 10-094A
Status last verified: Sep 2017
First submitted: 17 Feb 2010
Last updated: 25 Oct 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Multiple Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis
ClinicalTrials.gov ID: NCT01071512
Acronym / sponsor ID: 10-094A
Conditions: Multiple Sclerosis
Keywords: MRI, OCT, Tysabri, Multiple Sclerosis, cognition
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: University of ChicagoUniversity, hospital or other
Collaborators: Biogen
Study start: Apr 2010
Primary completion: Jan 2016 (actual)
Study completion: Jan 2016 (actual)
First posted: 19 Feb 2010 (estimated)
Results: Posted 6 Sep 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Tysabri	Experimental	Drug: TysabriNatalizumab 300 mg IV every 4 weeks

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TysabriAlso: NatalizumabInfuse 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.	Drug	Tysabri

Primary outcome

Change in Cognitive Function Over Time
Time frame: 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.

4 secondary outcomes

Change Over Time in Retinal Nerve Fiber Layer Thickness
Time frame: Baseline, 24, 48, 72, and 96 weeks
Change Over Time in Brain Parenchymal Fraction
Time frame: Baseline, 48 weeks, 96 weeks
Change Over Time in Normalized Thalamic Volume
Time frame: Baseline, 48 weeks, 96 weeks
Change Over Time in Normalized Hippocampal Volume
Time frame: Baseline, 48 weeks, 96 weeks

Results and safety

Results posted to the registry on 6 Sep 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tysabri	20	15

Primary outcome: Change in Cognitive Function Over Time

Time frame: Baseline, 48 weeks, 96 weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	Tysabri n = 15
Baseline	-1.5 (0.9)
Week 48	-1.2 (1.0)
Week 96	-1.2 (0.9)

Tysabri: p = 0.17, Mixed Models Analysis

Population analysed: Summary statistics are based on the 15 subjects who completed treatment

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 96 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tysabri	0 of 20 (0%)	1 of 20 (5%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jacqueline Bernard, M.D. principal investigator

University of Chicago

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Tysabri in people with Multiple Sclerosis, run by University of Chicago at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Cognitive Function Over Time (time frame: Baseline, 48 weeks, 96 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01071512.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2017.