Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Monastir
Sponsor:
Information provided by (Responsible Party):
Nouira, University of Monastir
ClinicalTrials.gov Identifier:
NCT02167165
First received: June 16, 2014
Last updated: NA
Last verified: June 2014
History: No changes posted
  Purpose

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 Intervention
Atrial Fibrillation
Drug: Digoxin

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Monastir:

Primary Outcome Measures:
  • Correlation between the response to digoxin and the genotypes of the patients [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    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:
  • Rhythm and Rate control [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    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:
  • Arterial hypotension Bradycardia (HR <45 bpm) Other (chest pain, allergic reaction……) [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

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.


Estimated Enrollment: 150
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Digoxin and AF
Patients consulting the emergency deprtment (ED) for AF and receiving Digoxin treatment
Drug: Digoxin
Patients consulting the ED for Acute onset AF received 0.5 mg digoxin by oral root

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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All patients presenting at the ED with acute onset AF documented by ECG.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02167165

Contacts
Contact: Semir Nouira, Professor +21673532014 semir.nouira@rns.tn

Locations
Tunisia
university of Monastir Recruiting
Monastir, Tunisia, 5000
Contact: Nouira Samir, Professor    73532014 ext +216    semir.nouira@rns.tn   
Principal Investigator: Nouira Samir, Professor         
Sponsors and Collaborators
University of Monastir
Investigators
Principal Investigator: Nouira Samir, Professor University of Monastir
  More Information

Additional Information:
No publications provided

Responsible Party: Nouira, Professor, University of Monastir
ClinicalTrials.gov Identifier: NCT02167165     History of Changes
Other Study ID Numbers: AF/DIGOXIN
Study First Received: June 16, 2014
Last Updated: June 16, 2014
Health Authority: Tunisia: Ministry of Public Health

Keywords provided by University of Monastir:
Atrial Fibrillation
Digoxin
SNP

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Digoxin
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014