Assessing Induction of Type II (M2) Monocytes/Macrophages in Patients Receiving Gilenya.

Study Overview
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Brief Summary
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In this study we wish to test the hypothesis that continuous Gilenya treatment alters immune homeostasis in favor of an anti-inflammatory type II monocyte and macrophage (M2) phenotype in the circulation of patients with relapsing-remitting Multiple Sclerosis (MS). In this study we will determine the change in ratio of M2 (type II, alternatively activated) versus M1 (type I, classically activated) monocytes and macrophages in a cohort of patients that have received continuous Gilenya treatment for 0, 1, 3, 6 or 12 months. We will also assess changes in cell surface expression of the M1 marker CCR7 and the M2 markers CD206 or CD301 by monocytes and macrophages using FACS analysis of whole blood, and assess the tyrosine phosphorylation of the signal transducer and activator of transcription STAT-1 (pTyr-STAT1), which is critical for the activation of M1 myeloid cells. We will assess correlates with changes in M1 and M2 cytokine expression assessing possible mechanisms of action of Gilenya on myeloid lineage cells.

Official Title
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Assessing Induction of Type II (M2) Monocytes/Macrophages in Patients Receiving Gilenya.

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Gilenya


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must qualify to receive treatment with Gilenya, according to the University of Southern California, Department of Neurology, MS Group, Gilenya Prescribing Process. Clinically definite Multiple Sclerosis defined by the revised McDonald criteria (Polman et al., 2005, Polman et al., 2010) of the relapsing-remitting form with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5. Ability to understand and sign this study-specific institutional review board-approved informed consent form. Willing to donate  50mls of blood for immunological testing on up to five occasions. Exclusion Criteria: Patient does not qualify to receive treatment with Gilenya, according to the USC, Department of Neurology, MS Group, Gilenya Prescribing Process. Inability to understand nature of the study. Treatment with any of the following within 30 days of commencing treatment with Gilenya: Avonex, Betaseron, Rebif, Copaxone, Natalizumab, Rituximab, Mitoxantrone, Cyclophosphamide, Cyclosporine, Azathioprine, Methotrexate or any other immunomodulatory, immunosuppressant or immune homeostasis altering drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gilenya treated - 1 month<br>Patient's taking continuous oral Gilenya at prescribed dose for 1 month. | Drug: Gilenya<br> <br> |
| Gilenya treated - 3 months<br>Patient's taking continuous oral Gilenya at prescribed dose for 3 months. | Drug: Gilenya<br> <br> |
| Gilenya treated - 6 months<br>Patient's taking continuous oral Gilenya at prescribed dose for 6 months. | Drug: Gilenya<br> <br> |
| Gilenya treated - 12 months<br>Patient's taking continuous oral Gilenya at prescribed dose for 12 months. | Drug: Gilenya<br> <br> |
| Gilenya qualified - untreated<br>Patient's qualifying to start treatment with oral Gilenya at prescribed dose but still as yet untreated. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ratio of M2 versus M1 monocytes and macrophages. |  | 12 months |