Mechanistic Studies of Teriflunomide in RRMS

December 23, 2022 updated by: Yang Mao-Draayer, University of Michigan

Mechanistic Studies of Teriflunomide in Relapsing Remitting Multiple Sclerosis: Regulatory B Lymphocytes as Central Mediators of the Therapeutic Effects of Teriflunomide in MS

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Observational

Enrollment (Actual)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

A total of 20 multiple sclerosis (MS) patients and 10 healthy controls will be recruited to voluntarily donate blood for the study. Blood samples will be collected prior to starting teriflunomide treatment (baseline) and after 3, 6, 9, 12, 18 and 24 months of treatment (+/- 2 weeks).

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
Patients with RRMS who have been newly prescribed Teriflunomide.
Drug: Teriflunomide
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.
Other Names:
  • Aubagio
2
Healthy Controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in frequency of regulatory and effector B cell subset
Time Frame: From baseline to 6 months and 12 months
Compare aubagio treatment to baseline and to healthy controls
From baseline to 6 months and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in frequency of CD4+ Th17, Th1, Th2, and Treg cells
Time Frame: From baseline to 6 months and 12 months
Compare aubagio treatment to baseline and to healthy controls
From baseline to 6 months and 12 months
Change in chemokine levels
Time Frame: From baseline to 6 months and 12 months
Compare aubagio treatment to baseline and to healthy controls
From baseline to 6 months and 12 months
Change in cytokine levels
Time Frame: From baseline to 6 months and 12 months
Compare aubagio treatment to baseline and to healthy controls
From baseline to 6 months and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Investigators

  • Principal Investigator: Yang Mao-Draayer, MD/PHD, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2018

Primary Completion (Actual)

October 13, 2021

Study Completion (Actual)

October 13, 2021

Study Registration Dates

First Submitted

March 7, 2018

First Submitted That Met QC Criteria

March 7, 2018

First Posted (Actual)

March 14, 2018

Study Record Updates

Last Update Posted (Actual)

December 27, 2022

Last Update Submitted That Met QC Criteria

December 23, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00136966

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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