Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Teriflunomide, B cell, T cell, cytokines
Brief summary
This study is to address the mechanism of action of teriflunomide in a phase IV open label trial with Teriflunomide in multiple sclerosis. Researchers will recruit 20 relapsing remitting multiple sclerosis patients (Group 1) start on treatment with teriflunomide (Aubagio). Patients will be enrolled from the Multiple Sclerosis Center at the University of Michigan Health System in Ann Arbor. Meanwhile, 10 healthy controls will be recruited, to establish a healthy baseline for B and T cells, which are affected by both MS and its treatment (Group 2). This Study will collect baseline pre-treatment blood samples periodically for up to 2 years. Blood biomarker changes will be correlated with clinical response to teriflunomide treatment intervention.
Detailed description
Multiple sclerosis is the most common autoimmune inflammatory and debilitating chronic demyelinating disease of the central nervous system mainly affecting young adults. There is a tremendous need to understand the mechanism of action of the treatment and how they might work in multiple sclerosis patients. Most recently, teriflunomide (AubagioTM) has been demonstrated to act as an immune modulatory therapy for patients with multiple sclerosis. Although one biochemical mechanism of action is understood to be related to inhibition of dihydroorotate dehydrogenase (DHODH) which affects synthesis of pyrimidine nucleotides, there have also been reports that the functions of regulatory T cells are promoted by these drugs independent of DHODH. Much accumulating evidence suggests that specialized subsets of B lymphocytes are important inducers of regulatory T cells, as well as having killer functions that may preferentially target TH1 and TH17 cells. This study aims to address the mechanism of action of teriflunomide in a phase IV open label trial with Teriflunomide in multiple sclerosis
Interventions
DRUGTeriflunomide
AUBAGIO® (teriflunomide) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), which inhibits pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase.
Sponsors
University of Michigan
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Patients with clinically-defined relapsing-remitting MS (RRMS) who are newly starting on teriflunomide (AubagioTM) at the time of enrollment have no evidence of relapse or corticosteroid treatment use within 2 months prior to enrollment OR Healthy controls who do not have a significant medical condition such as cancer, chronic infection, or autoimmune disease, have not taken steroids in the past 2 months, and who are not on an immune suppressant medication. 2. Ability to give informed consent 3. Willing to have blood drawn as scheduled in the protocol 4. Willing and able to complete all procedures and evaluations related to the study
Exclusion criteria
1. Medical or psychiatric conditions that may affect the patient's ability to give informed consent 2. Has received an experimental drug within 30 days of enrollment 3. Concomitant other disease modifying medications (such as Rebif, Betaseron, Avonex, Copaxone, Gilenya, Tecfidera, Alemtuzumab, methotrexate, azathioprine, mitoxantrone, cyclophosphamide, cyclosporine, natalizumab, rituxan, ocrelizumab, etc.) without the minimal washout period stated below: rebif, betaseron, avonex, copaxone within 1 month zinbryta, plegridy, gilenya, tecfidera within 2 months natalizumab within 3 months immunosuppressive/chemotherapeutic medications (e.g. azathioprine, methotrexate) within 6 months cyclophosphamide within 1 year rituximab, ofatumumab, ocrelizumab, cladribine within 1 year alemtuzumab at any time any mitoxantrone during previous 2 years prior to randomization or evidence of cardiotoxicity following mitoxantrone or a cumulative life-time dose of more than 60 mg/m2 lymphoid irradiation, bone marrow transplantation or other immunosuppressive treatments with effects potentially lasting over 6 months, at any time 4. Has any contraindication to high-dose immunotherapy, including pregnancy, trying to become pregnant, or breast feeding during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in frequency of regulatory and effector B cell subset | From baseline to 6 months and 12 months | Compare aubagio treatment to baseline and to healthy controls |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in frequency of CD4+ Th17, Th1, Th2, and Treg cells | From baseline to 6 months and 12 months | Compare aubagio treatment to baseline and to healthy controls |
| Change in chemokine levels | From baseline to 6 months and 12 months | Compare aubagio treatment to baseline and to healthy controls |
| Change in cytokine levels | From baseline to 6 months and 12 months | Compare aubagio treatment to baseline and to healthy controls |
Countries
United States
Outcome results
None listed