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Deficient T Regulatory Cell (Treg) Function in Patients With Relapsing Remitting Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT04857489
Recruitment Status : Recruiting
First Posted : April 23, 2021
Last Update Posted : April 23, 2021
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University

Brief Summary:
The purpose of this research is to find out how the T regulatory (Treg) cells control autoimmune response in multiple sclerosis. We will identify Treg molecular markers and changes in function in patients with relapse remitting multiple sclerosis (RRMS). We plan to study T regulatory immune cells in the blood of RRMS patients and control subjects to examine how Treg immune cells' deficient function may be involved in the development of mulitple sclerosis.

Condition or disease
Relapse Remitting Multiple Sclerosis

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Deficient T Regulatory Cell (Treg) Function in Patients With Relapsing Remitting Multiple Sclerosis
Actual Study Start Date : June 1, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Group/Cohort
Patients with Relapse Remitting Multiple Sclerosis
Blood sample
Healthy Controls
Blood Sample



Primary Outcome Measures :
  1. Characterize natural (n) Tregs' functional deficit in RRMS [ Time Frame: Baseline ]
    Functional suppression assays will compare Treg suppressive function in a third cohort of 10 HC and 10 RRMS patients.

  2. Identify the role of inducible (i) Treg cells in maintaining the immunological tolerance in RRMS [ Time Frame: Baseline ]

Secondary Outcome Measures :
  1. Identify the phenotype changes in CD4+CD25+CD127 nTregs in RRMS patients [ Time Frame: Baseline ]
    Transcriptional profiling of sorted CD4+CD25+CD127- Tregs will be performed using RNAseq in the first cohort of 10 HCs and 10 RRMS patients.

  2. Characterize functional deficits of nTregs in RRMS [ Time Frame: Baseline ]
    Functional suppression assays will compare Treg suppressive function in a third cohort of 10 HC and 10 RRMS patients.

  3. Determine the effects of hemostatic cytokines on the nTregs' suppressive function in RRMS [ Time Frame: Baseline ]
  4. Determine the phenotype of iTreg cells in RRMS [ Time Frame: Baseline ]
    Flow cytometry studies of the IL-10+CD4+ and TGF-B+CD4+ cells derived from RRMS patients and HCs will identify disease-specific phenotype of iTregs, which may reflect functional changes of iTregs in RRMS.

  5. Identify the mechanisms of deficient nTreg induction of iTregs in RRMS [ Time Frame: Baseline ]
    We will perform the suppressive assay using CD4+CD25+CD127-Treg and CD4+CD25-CD127+ Teff cells derived from the fourth cohort of 10 HCs and 10 RRMS patients.

  6. Characterize the effect of the iTreg-produced immunoregulatory cytokines on the reconstitution of immune tolerance [ Time Frame: Baseline ]
    We will measure the IFN-y, IL-17A, IL-17F, IL-21, IL-22, IL-9, and IL-10, TGF-B and IL-35 levels in the SNs of the above co-cultures of iTregs and CD4+ cell derived from RRMS patients and HCs at 48 h.


Biospecimen Retention:   Samples With DNA
Blood sample


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
40 Patients with relapse remitting multiple sclerosis (RRMS), 40 Healthy Controls
Criteria

Inclusion Criteria:

  • The inclusion criteria are confirmed diagnosis of RRMS according to McDonald's diagnostic criteria, age 18-55 inclusive, extended disability status score (EDSS) 1.5-5.5, and no immunomodulatory therapy at the time of the study. Treatment-free period will be at least 4 weeks for IV Methylprednisolone, Interferon-beta, Glatiramer acetate, Fingolimod, Tecfidera and Natalizumab. Patients previously treated with immunosuppressive therapies, including Azathioprine, Methotrexate, Mitoxantrone and Cyclophosphamide will not be enrolled in the study.

Exclusion Criteria:

  • Exclusion criteria will include concomitant infection, significant medical and psychiatric condition at the discretion of principal investigator. Pregnant women, and patients participating in other research trials will not be enrolled in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04857489


Contacts
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Contact: Silva Markovic-Plese, MD, PhD 215-503-6393 Silva.Markovic-Plese@jefferson.edu

Locations
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United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Silva Markovic-Plese, MD, PhD    215-503-6393    Silva.Markovic-Plese@jefferson.edu   
Sponsors and Collaborators
Thomas Jefferson University
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Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT04857489    
Other Study ID Numbers: 19S.016
First Posted: April 23, 2021    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases