Clinical trial NCT02167165: Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients
Official title: Role of Genetic Factors in the Response to Digoxin in the Acute Treatment of Atrial Fibrillation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Digoxin
SNP
Lead sponsor: University of Monastir
Sponsor class: OTHER
First posted: 2014-06-18
Enrollment: 150
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients presenting at the ED with acute onset AF documented by ECG.

Brief summary: This study tested the hypothesis that response to digoxin is modulated by single Nucleotid Polymorphism (SNP):

* Multi Drug Resistance (MDR1) gene haplotypes and Solute carrier organic anion transporter family member 1B3 (SLCO1B3) gene Polymorphism and their role in the response to treatement.
* Aldosterone synthase (CYP11B2) gene and sodium channel, voltage-gated, type V alpha subunit gene (SCN5A) correlated with atrial fibrillation and their roles in response to digoxin.

Detailed description: The frequency distribution of single nucleotide polymorphisms (SNPs) and haplotypes in the ABCB1 and SLCO1B3 genes varies largely among populations. The aim of this study is to investigate the genomic variations influence of these two genes on the response to digoxin in Tunisian atrial fibrillation (AF) patients.

In fact human P-glycoprotein (P-gp) is encoded by the ABCB1 gene (MDR1), which is located on chromosomal region 7q21 and consists of 28 exons. To date, over 50 SNPs have been reported for this gene, some of them are known to be of functional relevance and can also alter the pharmacokinetics of substrate drugs. The aim of the current study is to analyze the ABCB1: C1236T (Gly412Gly), G2677\>T⁄A (Ala893Ser/ Thr) and C3435T (Il1145Ile) polymorphisms.

SLCO1B3 (OATP1B3) gene located on chromosomal region 12p12 is highly polymorphic. It is known to transport digoxin and expressed on the sinusoidal membranes of hepatocytes in humans. It mediated uptake into hepatocytes and may be an important step of the elimination of digoxin. In this study we will also investigate the relationship between two deletion polymorphisms (from -28 to -11 deletion) and (from-7 to -4 deletion), T334G (Ser112Ala) and G699A (Met233Ile) SNPs in the SLCO1B3gene and their role in response to digoxin.

Another way, progress in understanding molecular mechanisms in AF supports the idea that variability in response to drug therapy may reflect differences in disease mechanisms, it is entirely possible that response to AF is highly heterogeneous because the arrhythmia itself is not a single pathophysiologic entity.

Aldosterone synthase (CYP11B2) gene polymorphism was found to be correlated with atrial fibrillation (AF) risk. Moreover, the human cardiac sodium channel SCN5A is responsible for the fast depolarization upstroke of the cardiac action potential and serves as a molecular target for antiarrhythmic drugs. Mutations in the human cardiac sodium channel gene have been previously discovered in a spectrum of cardiac rhythm disorders. We hypothesized that the T-344C and H558R (His558Arg) SNPs in CYP11B2 and SCN5A gene which are associated with susceptibility to AF could be implicated in the variation of response to Digoxin.

Eligibility criteria: Inclusion Criteria:

* Patients older than 20 years
* Quick AF (heart rate\> 120 bpm) diagnosed by ECG

Exclusion Criteria:

* HR under 120 bpm
* Hemodynamically unstable patients
* Atrio-Ventricular-block (second or third degree)
* Ventricular rhythm disorder
* Acute coronary syndrome
* kidney failure
* Hypokalimia

Primary outcomes:
measure: Correlation between the response to digoxin and the genotypes of the patients
timeFrame: 24 hours
Secondary outcomes:
measure: Rhythm and Rate control
timeFrame: 24 hours
Other outcomes:
measure: Arterial hypotension Bradycardia (HR <45 bpm) Other (chest pain, allergic reaction……)
timeFrame: 24 hours
Locations:
city: Monastir
country: Tunisia
facility: university of Monastir
Study officials:
affiliation: University of Monastir
name: Nouira Samir, Professor
role: PRINCIPAL_INVESTIGATOR
References: