Action of the Vidaza on the Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— AVIFA  

Official title:

Action of the Vidaza on the Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03298321
• Other study ID #: 69HCL17_0114
• Status: Recruiting
• Start date: December 20, 2018
• Est. completion date: December 20, 2021

Study information

• Verified date: October 2019
• Source: Hospices Civils de Lyon
• Contact: Philippe CHEVALIER, MD
• Phone: 04 72 35 76 89
• Email: philippe.chavalier[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Genomic studies on atrial fibrillation patients have identified polymorphisms in regions surrounding the PITX2 gene, suggesting it could be the locus responsible for atrial fibrillation. The PITX2 gene is essential for establishing the asymmetry between systemic and pulmonary blood flow, which is absolutely required for proper heart functions. In addition, PITX2 is required for the development the atrium myocardium. Investigators have performed transcriptomic analysis on left atrium tissues from atrial fibrillation patients and identify genes whose expression is altered in atrial fibrillation. Among affected genes, PITX2 expression is strongly decreased in the left atrium of atrial fibrillation patients. Moreover, investigators observed that the PITX2 promoter region is hypermethylated in atrial fibrillation patients. Interestingly, DNA methylation is a key actor of gene expression and directly regulates RNA transcription either by directly modulating transcription factor (TF) binding to gene promoters or by modifying local chromatin structures, therefore limiting access of TFs to DNA. These epigenetic modifications are reversible and therefore represent an interesting therapeutic target. Hence, many compounds that inhibit DNA methyl-transferase are currently tested in different disease models. Recently-designed hypomethylating molecules are available, such as the 5'azacytidine (Vidaza®, Celgen Inc.) or the 5-aza-2'-deoxycytidine (Decitabine) (Dacogen®, Janssen Cilag). Investigators have performed preliminary studies on the effect of Decitabine on DNA methylation and proper cardiac function recovering in a SHR model. Results indicate that the chronic delivery of Decitabine improves the arrhythmia profile by reducing tachyarrhythmia, fibrosis, as well as the oxidative stress in SHR left atrium submitted Acute Leukemia is a rare pathology with an incidence of 4 per 100,000 in France. Azacytidine, which is closely related to Decitabine, is commonly used for treating Acute Leukemia and possesses anti-neoplastic effect through multiple mechanisms, including direct cytotoxicity of blood cancer cells and DNA hypomethylation. The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis as well, which are the two mains phenotypic manifestation of atrial fibrillation in humans. Investigators hypothesize that azacytidine decreases PITX2 promoter methylation and increases PITX2 expression. Hence, investigators expect to ameliorate the duration of atrium action potential and to observe a decrease of atrium fibrosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: December 20, 2021
• Est. primary completion date: December 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years old

• Patient with history of paroxysmal atrial fibrillation, and /or presenting a dilatation of the left atrium.

• Patient selected for a first Vidaza® treatment

• Non-opposition of the patient to participate in the study

Exclusion Criteria:

• Age < 18 years old

• No paroxysmal atrial fibrillation

• Patients with previous history of Vidaza® treatment

Related Conditions & MeSH terms

• Acute Leukemia
• Atrial Fibrillation

Intervention

Other:
• Effect of Vidaza treatment
The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis.

Locations

Country	Name	City	State
France	Service de rythmologie - GH Est-Hôpital Louis Pradel - CHU de Lyon HCL	Bron
France	Centre Léon Berard	Lyon
France	Hopital Lyon Sud	Pierre-Bénite

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evolution of atrial arrhythmic events	Evolution of the atrial arrhythmic events observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by Holter-ECG.	Maximum 12 months
Secondary	Evolution of the morphology and the fibrosis atrial	Evolution of the morphology and the fibrosis atrial observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by transthoracic echocardiography.	Maximum 12 months