- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02167165
Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients
Role of Genetic Factors in the Response to Digoxin in the Acute Treatment of Atrial Fibrillation
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.
Study Overview
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Monastir, Tunisia, 5000
- University of Monastir
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Digoxin and AF
Patients consulting the emergency deprtment (ED) for AF and receiving Digoxin treatment
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Patients consulting the ED for Acute onset AF received 0.5 mg digoxin by oral root
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation between the response to digoxin and the genotypes of the patients
Time Frame: 24 hours
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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;
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24 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rhythm and Rate control
Time Frame: 24 hours
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Rhythm control: rate and delay of return to sinusal rhythm.
Rate control: reduction of heart rate : HR <100 bpm or 20% reduction from baseline
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24 hours
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Arterial hypotension Bradycardia (HR <45 bpm) Other (chest pain, allergic reaction……)
Time Frame: 24 hours
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hypotension during hospitalisation, bradycardia, chest pain, allergic reaction
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24 hours
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Nouira Samir, Professor, University of Monastir
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AF/DIGOXIN
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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