Immunoregulatory Effect of Microparticle Delivered STING Agonist in the Control of Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS)

January 20, 2023 updated by: Thomas Jefferson University
Microparticles (MPs) as a mode of therapeutic delivery can selectively deliver immunomodulatory treatment to the phagocytic cells, particularly dendritic cells (DCs), inducing their tolerogenic phenotype and function and T regulatory (Treg) cell expansion. The study will characterize the in vitro response of cGAMP immunomodulator incapsulated microparticles on the capacity of DCs and Tregs to regulate the inflammatory response.

Study Overview

Status

Recruiting

Intervention / Treatment

Detailed Description

This is a lab study only. No medication will be dispensed as a part of the study. No tests or procedures will be performed. Blood ( approximately 10 teaspoons ; 10 green top tubes) will be drawn by a qualified phlebotomist, nurse or physician in the Neurology clinic, during routine clinic visits. Proper medical procedures will be followed when collecting blood to minimize patient risk. In addition, steps will be taken to guard patient's confidentiality. Unique codes will be assigned to each sample. All identifying information will be removed from samples and clinical data before they are given to the research staff conducting the laboratory study. Only the clinic staff will have access to the consent forms, the master list (that connect the unique codes with the patient names) and subject medical records. The blood draw will coincide with the subject's regular visit to the Neurology clinic.

All records will be secured with the current PACS radiology system and computerized information systems/computerized databases which are the current methods for securing all patient information. Care will be taken to preserve the confidentiality of all patient-related information. Material with identifying information will be stored in the clinic locked data storage room. Patient names will not be used in any publications. Results of laboratory studies performed on these samples will not be shared with subjects. Laboratory results will not be incorporated into patients medical records.

The proposal states to separate dendritic cells using magnetic beads separation and use them as an antigen presenting cells to T cells.The therapeutic effect of the nanoparticle delivered phosphatidylserine (PS, PAR-PS) will be measured, using cytokine secretion and the detection of the T regulatory (Treg) cell induction. Proliferation will be determined using CFSE, cytokine secretion will be measured using ELISA and the intracellular cytokine staining for IFNg, IL-17A, IL-17F, IL-21, IL-22, TGFb, IL-10 and IL-4. The induction of Treg cells will be measured using flow cytometry and determining the percentage of CD4+ CD25+ CD127- FoxP3+ Treg cells within the CD4+ lymphocytes.

Study Type

Observational

Enrollment (Anticipated)

40

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

    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University
        • Principal Investigator:
          • Silva Markovic-Plese, MD, PhD

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 55 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

40 patients diagnosed with relapse remitting multiple sclerosis

Description

Inclusion Criteria:

  1. Subjects meeting diagnostic criteria for relapsing remitting multiple sclerosis
  2. Between the ages of 18-55
  3. Not treated with immunomodulatory therapy, no other neurological diagnosis, no other inflammatory disease

Exclusion Criteria:

-

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterize cGAMP MP-induced tolerogenic DCs from RRMS patients.
Time Frame: Baseline
Flow cytometry study will measure the cGAMP MP phagocytosis by PBMCs and characterize the phenotype of cGAMP MP-induced DCs of 40 untreated RRMS patients after incubation with fluorescently-labelled cGAMP MPs.
Baseline
Determine the capacity of cGAMP MP-treated DCs to induce iTreg expansion in human in-vitro cultures
Time Frame: Baseline
Flow cytometry studies will characterize the induced Treg phenotype generated after co-culture with cGAMP MP-treated DCs cells to determine the capacity of the cGAMP MP-treated DCs to induce differentiation and expansion of iTregs
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the transcriptome of cGAMP MP IL-27- and IL-10-induced Tregs.
Time Frame: Baseline
RNA sequencing of iTreg cells after coculture with cGAMP MP-treated (vs. blank MP-treated) DCs from 10 RRMS patients will detect the differentially expressed genes between cGAM MP- and blank MP-induced iTregs. The expression of transcription factors identified by RNAseq will be confirmed by RT-PCR and western blot, more quantitative methods.
Baseline
Determine the in-vitro reconstitution of iTreg suppressive function in RRMS patients after coculture with cGAMP MP-treated DCs.
Time Frame: Baseline
Suppression assay will determine to what extent Treg cells from co-cultures with cGAM-MP-treated DCs increase (restore normal) suppressive function in comparison to the co-cultures with blank MP-treated DCs.
Baseline
Induction of antigen-specific immune tolerance after co-administer DR2-aAPMs with the cGAMP MPs to DCs.
Time Frame: Baseline
The suppressive effect of sorted Tregs induced after co-administration of cGAMP MPs and DR2-APM to monocyte-derived DCs, will be tested in co-cultures with autologous T effector cells. Myelin antigen specificity will be determined in Teff and iTreg cells by MHCII tetramer staining.
Baseline

Collaborators and Investigators

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

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)

February 26, 2021

Primary Completion (ANTICIPATED)

May 1, 2024

Study Completion (ANTICIPATED)

May 1, 2024

Study Registration Dates

First Submitted

April 20, 2021

First Submitted That Met QC Criteria

January 20, 2023

First Posted (ACTUAL)

January 31, 2023

Study Record Updates

Last Update Posted (ACTUAL)

January 31, 2023

Last Update Submitted That Met QC Criteria

January 20, 2023

Last Verified

January 1, 2023

More Information

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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