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

Demyelinating Autoimmune Diseases, CNS Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02862301
• Other study ID #: API/2015/64
• Status: Recruiting
• Phase: N/A
• Start date: April 2016
• Est. completion date: September 2020

Study information

• Verified date: November 2019
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: Matthieu Béreau, MD
• Email: mbereau[@]chu-besancon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: September 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Autoimmune Diseases
• Demyelinating Autoimmune Diseases, CNS

Intervention

Biological:
• blood sample

Locations

Country	Name	City	State
France	University Hospital	Besançon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HDAC/ HAT enzymatic activity (ratio)		day of inclusion