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Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients

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ClinicalTrials.gov Identifier: NCT02167165
Recruitment Status : Completed
First Posted : June 18, 2014
Last Update Posted : February 12, 2020
Information provided by (Responsible Party):
Pr. Semir Nouira, University of Monastir

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.

Condition or disease Intervention/treatment
Atrial Fibrillation Drug: Digoxin Injection

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.

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Study Type : Observational
Actual Enrollment : 150 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Role of Genetic Factors in the Response to Digoxin in the Acute Treatment of Atrial Fibrillation
Actual Study Start Date : July 2013
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Group/Cohort Intervention/treatment
Digoxin and AF
Patients consulting the emergency deprtment (ED) for AF and receiving Digoxin treatment
Drug: Digoxin Injection
Patients consulting the ED for Acute onset AF received 0.5 mg digoxin by oral root

Primary Outcome Measures :
  1. Correlation between the response to digoxin and the genotypes of the patients [ Time Frame: 24 hours ]
    In the current study we aimed at outlining the different MDR-1, SLCO1B3, CYP11B12 and SCN5A genotypes in a sample of Tunisian patients, suffering from AF and taking digoxin, to assess the role of SNPs in affecting serum digoxin concentrations, and studying the consequences on patients' clinical outcome. Patients will be monitored for 24 hours in an intensive care unit;

Secondary Outcome Measures :
  1. Rhythm and Rate control [ Time Frame: 24 hours ]
    Rhythm control: rate and delay of return to sinusal rhythm. Rate control: reduction of heart rate : HR <100 bpm or 20% reduction from baseline

Other Outcome Measures:
  1. Arterial hypotension Bradycardia (HR <45 bpm) Other (chest pain, allergic reaction……) [ Time Frame: 24 hours ]
    hypotension during hospitalisation, bradycardia, chest pain, allergic reaction

Biospecimen Retention:   Samples With DNA
arterial blood samples collected in EDTA tubes and stored in - 20°C envirement for DNA extraction with salting out methods.

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients presenting at the ED with acute onset AF documented by ECG.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02167165

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university of Monastir
Monastir, Tunisia, 5000
Sponsors and Collaborators
University of Monastir
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Principal Investigator: Nouira Samir, Professor University of Monastir
Additional Information:
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Responsible Party: Pr. Semir Nouira, Professor, University of Monastir
ClinicalTrials.gov Identifier: NCT02167165    
Other Study ID Numbers: AF/DIGOXIN
First Posted: June 18, 2014    Key Record Dates
Last Update Posted: February 12, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pr. Semir Nouira, University of Monastir:
Atrial Fibrillation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Anti-Arrhythmia Agents
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs