Clinical trial NCT01626248: Analysis of Lymphocyte Cell Surface Adhesion Marker Expression in Natalizumab Population With Active Control
Official title: Analysis of Lymphocyte Cell Surface Adhesion Marker Expression in a Natalizumab Treated Population With Active Control Assessment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: Immunological
biomarkers
observational
RRMS
Relapsing
Remitting Multiple Sclerosis
Lead sponsor: Rocky Mountain MS Research Group, LLC
Sponsor class: OTHER
Collaborators: name: Biogen
name: Elan Pharmaceuticals
First posted: 2012-06-22
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Relapsing Remitting Multiple Sclerosis (RRMS) who are treated at Rocky Mountain Multiple Sclerosis Clinic, and who are currently undergoing disease modifying therapy, natalizumab, glatiramer acetate injections, interferon beta 1a, or who are beginning one of these disease modifying therapies.

Brief summary: The purpose of the study is to research the association between receiving Tysabri® (natalizumab), interferon beta-1a, glatiramer acetate or not having any treatment for your MS and how it may or may not impact certain white blood cells and other immunological markers. This information may be useful in identifying risk factors in developing progressive multifocal leukoencephalopathy (PML). It does appear that the risk increases with the total number of natalizumab infusions. Patients who have not yet started a disease modifying therapy or who have been on one other than natalizumab are needed as controls to see how these biomarkers change.

Patients at various stages of natalizumab treatment as well as natalizumab naïve are needed to allow for analysis of the change in potential markers over time.

Detailed description: Patients at various timepoints in their MS treatment or who are beginning certain MS treatments will be consented and have blood specimens collected to allow for an immunological comparison. The decision to treat with disease modifying therapies is made independently from this observational study.

Primary endpoint: To further understand the delineation of lymphocyte cell adhesion marker down regulation within a treatment naïve patient population and at various stages of treatment.

Secondary endpoint: To understand the correlation between natalizumab pharmacodynamics, pharmacokinetics and lymphocyte cell adhesion marker down regulation.

The results of various biomarkers and immunological testing (including CD62L, LFA-1, sCD62L, sLFA-1, sVCAM, VLA-4 saturation, IgG4, CBC with absolute differential) will be compared amongst the groups consented. The treatment naive group will be compared longitudinally.

Eligibility criteria: Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Aged 18 to 80 years old, inclusive, at the time of informed consent.
3. Patients with a relapsing form of Multiple Sclerosis as determined by the treating or back-up neurologist per chart review.
4. If getting natalizumab or scheduled to commence natalizumab infusion the patient must be enrolled in the TOUCH Prescribing Program and who is not expected to discontinue Tysabri® therapy prior to completion of the requirements of this study or must be currently prescribed and using interferon beta 1a or glatiramer acetate injections for 18 months; or, naïve to natalizumab, interferon beta 1a or glatiramer acetate and beginning treatment after consent.
5. Patients screened for Group A must be completely naïve to natalizumab, patients beginning interferon beta-1a or glatiramer acetate must also be naïve to natalizumab.
6. Patients screened for natalizumab naïve must have at least 30 days clear of other disease modifying therapies.
7. Patients must be free of known systemic bacterial or viral infections.
8. No fever over 99.5 degrees Fahrenheit in the last two weeks or at Baseline or prior to any scheduled specimen collection.
9. No herpes zoster outbreaks within the last 30 days.
10. No methylprednisolone sodium succinate infusion (solumedrol) or corticosteroid use within the last 30 days.
11. Must weigh between 44 and 190 kg, inclusive.

Exclusion Criteria:

1. Patient is unwilling or unable, in the opinion of the investigator, to comply with study instructions.
2. Patients experiencing a MS relapse or exacerbation which results in methylprednisolone sodium succinate infusion 30 days prior to Baseline
3. Patients with active, unknown infection etiology - if a patient is being treated for a known infection this would be allowed at the discretion of the Investigator, but if they present with signs of infection that has not been diagnosed they should be excluded.
4. Fever of 99.6 or higher within the last two weeks prior to any of the scheduled specimen collection (Baseline, 1 month, 3 month, 12 month or 18 month).
5. If patient has missed doses of their DMT as per the inclusion criteria.
6. No prior immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil).
7. Specimen collection must occur Monday through Thursday.

Primary outcomes:
measure: Quantitative Assessment of CD62L in MS Patients on Immunomodulatory Agents
timeFrame: 12 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Rocky Mountain MS Clinic
state: Utah
Study officials:
affiliation: Rocky Mountain MS Research Group, LLC
name: John F Foley, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Harris VK, Sadiq SA. Disease biomarkers in multiple sclerosis: potential for use in therapeutic decision making. Mol Diagn Ther. 2009;13(4):225-44. doi: 10.1007/BF03256329.
citation: Rice GP, Hartung HP, Calabresi PA. Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology. 2005 Apr 26;64(8):1336-42. doi: 10.1212/01.WNL.0000158329.30470.D0.
citation: Shimada Y, Hasegawa M, Takehara K, Sato S. Elevated serum L-selectin levels and decreased L-selectin expression on CD8(+) lymphocytes in systemic sclerosis. Clin Exp Immunol. 2001 Jun;124(3):474-9. doi: 10.1046/j.1365-2249.2001.01514.x.