Epigenetic Evaluation of HAT/HDAC Activity in PBMC From Patients With Clinically Isolated Syndrome (EPIC)
Primary Purpose
Demyelinating Autoimmune Diseases, CNS
Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
blood sample
Sponsored by
About this trial
This is an interventional basic science trial for Demyelinating Autoimmune Diseases, CNS focused on measuring Histone Deacetylases, Histone Acetyltransferases
Eligibility Criteria
Inclusion Criteria:
- Clinically isolated syndrome within the last 6 weeks (CIS group)
- Healthy volunteer, free of any inflammatory disease (control group)
- Patient able to understand the reason of the study
- Signed informed consent
Exclusion Criteria:
- Pregnancy
- Systemic corticosteroid therapy (>1mg/kg)
- Immunosuppressive/immunomodulatory therapy (prior or ongoing) (CIS group)
- Patient with ongoing infection (Control group)
Sites / Locations
- University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Experimental
Arm Label
Control group
CIS group
Arm Description
Healthy volunteers, free of any inflammatory disease. A blood sample is performed on the day of inclusion.
patients with Clinically isolated syndrome. A blood sample is performed on the day of inclusion and after 3 months.
Outcomes
Primary Outcome Measures
HDAC/ HAT enzymatic activity (ratio)
Secondary Outcome Measures
Full Information
NCT ID
NCT02862301
First Posted
August 3, 2016
Last Updated
November 15, 2019
Sponsor
Centre Hospitalier Universitaire de Besancon
1. Study Identification
Unique Protocol Identification Number
NCT02862301
Brief Title
Epigenetic Evaluation of HAT/HDAC Activity in PBMC From Patients With Clinically Isolated Syndrome
Acronym
EPIC
Official Title
Epigenetic Evaluation of HAT/HDAC Activity in Peripheral Blood Mononuclear Cells From Patients With Clinically Isolated Syndrome and Analysis of the Relationship With the Pathophysiology and Disease Activity
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
April 2016 (undefined)
Primary Completion Date
June 2020 (Anticipated)
Study Completion Date
September 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Besancon
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of the study is to compare the enzymatic activity of HATs and HDACs in peripheral blood mononuclear cell (PBMC) of patients with a clinically isolated syndrome (CIS group) and healthy controls (control group).
Detailed Description
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS). Clinically isolated syndrome (CIS) is often a sign of multiple sclerosis and the term refers to the first episode of neurologic symptoms experienced by a patient. Possible presentations of CIS include optic neuritis, a brain stem and/or cerebellar syndrome, a spinal cord syndrome, or occasionally cerebral hemispheric dysfunction. An accurate diagnosis at this time is important because people with a high risk of developing MS are encouraged to begin treatment in order to delay or prevent a second neurologic episode and, therefore, the onset of MS.
The innate and adaptative immune systems play an important role in pathophysiology of MS, acting in interaction with environmental, genetic, and epigenetic factors.
Epigenetic modifications, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. Histone acetylation, through the family of histone acetyl transferase (HAT), is most consistently associated with promoting transcription. Deacetylation of histones correlates with CpG methylation and the inactive state of chromatin. There are 4 classes of histone deacetylase enzymes (HDACs), with members capable of deacetylation of histones and/or other protein targets. Acetylation homeostasis is a key regulator of both immune cell activation. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. This study could provide information on the mechanisms involved.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Demyelinating Autoimmune Diseases, CNS
Keywords
Histone Deacetylases, Histone Acetyltransferases
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control group
Arm Type
Other
Arm Description
Healthy volunteers, free of any inflammatory disease. A blood sample is performed on the day of inclusion.
Arm Title
CIS group
Arm Type
Experimental
Arm Description
patients with Clinically isolated syndrome. A blood sample is performed on the day of inclusion and after 3 months.
Intervention Type
Biological
Intervention Name(s)
blood sample
Primary Outcome Measure Information:
Title
HDAC/ HAT enzymatic activity (ratio)
Time Frame
day of inclusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Clinically isolated syndrome within the last 6 weeks (CIS group)
Healthy volunteer, free of any inflammatory disease (control group)
Patient able to understand the reason of the study
Signed informed consent
Exclusion Criteria:
Pregnancy
Systemic corticosteroid therapy (>1mg/kg)
Immunosuppressive/immunomodulatory therapy (prior or ongoing) (CIS group)
Patient with ongoing infection (Control group)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matthieu Béreau, MD
Email
mbereau@chu-besancon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthieu Béreau, MD
Organizational Affiliation
CHU de Besançon
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthieu Béreau, Doctor
Email
mbereau@chu-besancon.fr
12. IPD Sharing Statement
Plan to Share IPD
No
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Epigenetic Evaluation of HAT/HDAC Activity in PBMC From Patients With Clinically Isolated Syndrome
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