Clinical trial NCT05705986: Immunoregulatory Effect of Microparticle Delivered STING Agonist in the Control of Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS)
Official title: Immunoregulatory Effect of Microparticle Delivered STING Agonist in the Control of Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Relapse Remitting Multiple Sclerosis
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2023-01-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 40 patients diagnosed with relapse remitting multiple sclerosis

Brief summary: 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.

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.

Eligibility criteria: 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:

-

Primary outcomes:
measure: Characterize cGAMP MP-induced tolerogenic DCs from RRMS patients.
timeFrame: Baseline
measure: Determine the capacity of cGAMP MP-treated DCs to induce iTreg expansion in human in-vitro cultures
timeFrame: Baseline
Secondary outcomes:
measure: Determine the transcriptome of cGAMP MP IL-27- and IL-10-induced Tregs.
timeFrame: Baseline
measure: Determine the in-vitro reconstitution of iTreg suppressive function in RRMS patients after coculture with cGAMP MP-treated DCs.
timeFrame: Baseline
measure: Induction of antigen-specific immune tolerance after co-administer DR2-aAPMs with the cGAMP MPs to DCs.
timeFrame: Baseline
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
References: