Action of the Vidaza on the Atrial Fibrillation

NCT03298321 | Completed

• 1 other identifier: 69HCL17_0114
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Atrial Fibrillation; Acute Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Evolution of the morphology and the fibrosis atrial

  Maximum 12 months

Study Arms (1)

Vidaza patients

This study will be performed on adults with Acute Myeloid Leukemia and atrial fibrillation. Only patients treated for the first time with vidaza® within an hospital hematology unit will be included.

Other: Effect of Vidaza treatment

Interventions

Effect of Vidaza treatment OTHER

The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis.

Vidaza patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will be performed on adults with Acute Myeloid Leukemia and atrial fibrillation. Only patients treated for the first time with vidaza® within an hospital hematology unit will be included.

You may qualify if:

• 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

You may not qualify if:

• Age \< 18 years old
• No paroxysmal atrial fibrillation
• Patients with previous history of Vidaza® treatment

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (3)

Service de rythmologie - GH Est-Hôpital Louis Pradel - CHU de Lyon HCL

Bron, 69229, France

Location

Centre Léon Berard

Lyon, 69008, France

Location

Hopital Lyon Sud

Pierre-Bénite, 69310, France

Location

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 2, 2017
• Study Start: December 20, 2018
• Primary Completion: December 20, 2018
• Study Completion: December 20, 2018
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)