Efficacy of the Use of Genetic Markers in the Choice of the Pharmacological Treatment of Smoking (GENTSMOKING)
NCT ID: NCT03362099
Last Updated: 2022-12-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE4
361 participants
INTERVENTIONAL
2016-11-01
2022-04-15
Brief Summary
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Considering this scenario, some drugs are used in tobacco cessation therapy. The first-line anti-smoking treatments approved by the Food and drug administration ( FDA ) are nicotinic reuptake therapy, bupropion ( norepinephrine and dopamine reuptake inhibitor) and varenicline ( partial agonist of nicotinic receptors composed of subunits alpha4Beta2 ). A metanalysis of 16 clinical studies indicated that smokers treated with bupropion had a higher abstinence rate compared to those receiving placebo - Odds ratio (OR ) - of 1,97 for treatment success.
Varenicline is more effective compared to others smoking cessation drugs approved by the FDA, with an OR of 2,27 ( IC 95% 2,02-2,55 ) compared to placebo. However, Varenicline is much more expensive than bupropion.
Significant advances in genetics have made the variability of the individual response to drugs, as far as efficacy as well as the rate of adverse effects, begin to be specifically investigated through pharmacogenetics studies.
Detailed Description
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The polymorphisms in genes involved in the coding of metabolized drug enzymes, in the variability of carrier proteins or receptors are at the heart of these investigations. The gene CHRNA4 is an important gene for anti-smoking pharmacogenetics studies because they encode the alpha 4 beta 2 subunits of acetylcholine- nicotinic receptors ( which is important target for an action of varenicline ) and CYP2B6 major isoenzyme that metabolizes the bupropion. Rocha et al found the association of polymorphisms CHRNA4rs1044396 with success in smoking cessation in patients treated with varenicline and Tomaz et al found an association between CYP2B6rs2279343 and efficacy of bupropion.
Patients with the CC genotype, for the polymorphism CHRNA4rs1044396, had a lower success rate in treatment with varenicline( 29,5% ), compared to those with CT or TT genotypes (50,9% ) ( P =0,07 , n=167 ). The CT or TT genotypes were associated with a higher risk - Odds ratio ( OR ) - of success ( OR=1,67, IC 95%=1,10-2,53,P=0,02), in a multivariate model. Patients with the genotype AA, for the polymorphism CYP2B6rs2279343, obtained a higher success rate in treatment with bupropion ( 48,0% ), compared to patients with the AG or GG genotypes ( 35,5% ) (P=0,05,n=237). The AA genotype was associated with higher odds ratios for treatment success (OR=1,92,IC 95%=1,08-3,42,P=0,03) ,in a multivariate model.
It is suggested that these polymorphisms influence the pharmacological response and may be important for the design of an individualized pharmacotherapy.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Group Varenicline
Patients randomized to this group will collect polymorphisms at time zero and will receive varenicline for smoking cessation. The polymorphism result will only be known at the end of the protocol. Varenicline dosage 0,5 mg once a day for 3 days, after this 0,5 mg twice a day until seven day .At day eight 1 mg twice a day until complete week twelve.
No interventions assigned to this group
Group Genetic
The patients randomized to this arm will collect polymorphisms and could receive varenicline or bupropion or both depending on genetic polymorphisms for each one these drugs.
Bupropiona dosage 150 mg once a day seven days, after twice a day until complete week twelve. Varenicline dosage 0,5 mg once a day for 3 days, after this 0,5 mg twice a day until seven day .At day eight 1 mg twice a day until complete week twelve.
Varenicline Tartrate or bupropion
the drug treatment will be chosen related to the polymorphism. If the polymorphism is favorable to varenicline the patient will receive varenicline, If it is favorable to bupropion the patient will receive bupropion, if not favorable to varenicline and bupropion the patient will receive bupropion + varenicline. If the patient has both favorable polymorphisms he will receive bupropion. Bupropiona dosage 150 mg once a day seven days, after twice a day until complete week twelve. Varenicline dosage 0,5 mg once a day for 3 days, after this 0,5 mg twice a day until seven day .At day eight 1 mg twice a day until complete week twelve.
Interventions
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Varenicline Tartrate or bupropion
the drug treatment will be chosen related to the polymorphism. If the polymorphism is favorable to varenicline the patient will receive varenicline, If it is favorable to bupropion the patient will receive bupropion, if not favorable to varenicline and bupropion the patient will receive bupropion + varenicline. If the patient has both favorable polymorphisms he will receive bupropion. Bupropiona dosage 150 mg once a day seven days, after twice a day until complete week twelve. Varenicline dosage 0,5 mg once a day for 3 days, after this 0,5 mg twice a day until seven day .At day eight 1 mg twice a day until complete week twelve.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* unstable psychiatric disorders.
* In the treatment of neoplastic diseases.
* Limitation to attend the medical visits
18 Years
75 Years
ALL
Yes
Sponsors
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Fundação de Amparo à Pesquisa do Estado de São Paulo
OTHER_GOV
University of Sao Paulo General Hospital
OTHER
Responsible Party
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Jaqueline Scholz
Principal Investigator
Principal Investigators
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Jaqueline R Scholz, MD.Phd
Role: PRINCIPAL_INVESTIGATOR
Heart Institute - University of São Paulo - Braziil
Locations
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Ambulatório de Tratamento Tabagismo - Incor HCFMUSP
São Paulo, , Brazil
Countries
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References
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Tomaz PR, Santos JR, Issa JS, Abe TO, Gaya PV, Krieger JE, Pereira AC, Santos PC. CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy. Eur J Clin Pharmacol. 2015 Sep;71(9):1067-73. doi: 10.1007/s00228-015-1896-x. Epub 2015 Jul 8.
Rocha Santos J, Tomaz PR, Issa JS, Abe TO, Krieger JE, Pereira AC, Santos PC. CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy. Front Genet. 2015 Feb 27;6:46. doi: 10.3389/fgene.2015.00046. eCollection 2015.
Gaya PV, Fonseca GWP, Tanji LT, Abe TO, Alves MJNN, de Lima Santos PCJ, Consolim Colombo FM, Scholz JR. Smoking cessation decreases arterial blood pressure in hypertensive smokers: A subgroup analysis of the randomized controlled trial GENTSMOKING. Tob Induc Dis. 2024 May 16;22. doi: 10.18332/tid/186853. eCollection 2024.
Gaya PV, Santos JR, Tomaz PRX, Abe TMO, Nassif M Jr, Galas LG, Bellini BB, Moraes IR, Santos PCL, Correa PCRP, Scholz JR. Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING. Tob Induc Dis. 2024 Apr 16;22. doi: 10.18332/tid/186072. eCollection 2024.
Related Links
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CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy
CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy
Other Identifiers
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6013381600000068
Identifier Type: -
Identifier Source: org_study_id