Epigenetic Evaluation of HAT/HDAC Activity in PBMC From Patients With Clinically Isolated Syndrome (EPIC)

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

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).

Study Overview

• Status: Unknown
• Conditions: Demyelinating Autoimmune Diseases, CNS
• Intervention / Treatment: Biological: blood sample

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.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthieu Béreau, MD; Email: mbereau@chu-besancon.fr

Study Locations

• France
  • Besançon, France
    • Recruiting
    • University Hospital
    • Contact: Matthieu Béreau, Doctor; Email: mbereau@chu-besancon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control group; Healthy volunteers, free of any inflammatory disease. A blood sample is performed on the day of inclusion.	Biological: blood sample
Experimental: CIS group; patients with Clinically isolated syndrome. A blood sample is performed on the day of inclusion and after 3 months.	Biological: blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HDAC/ HAT enzymatic activity (ratio)	day of inclusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Principal Investigator: Matthieu Béreau, MD, CHU de Besancon

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Histone Deacetylases; Histone Acetyltransferases
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Leukoencephalopathies; Autoimmune Diseases; Demyelinating Autoimmune Diseases, CNS
• Other Study ID Numbers: API/2015/64

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO