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Efficacy of the Use of Genetic Markers in the Choice of the Pharmacological Treatment of Smoking (GENTSMOKE) (GENTSMOKE)

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ClinicalTrials.gov Identifier: NCT03362099
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Jaqueline Scholz, University of Sao Paulo General Hospital

Brief Summary:

Smoking is the leading cause of avoidable death in the world. Smoking is associated with the development of cardiovascular and respiratory diseases, as well as being considered a leading cause of cancer death. Data show that smokers have increased cardiovascular risk in relation to former smokers, even in comparison with individuals who have had a long and intense history tobacco use.

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.


Condition or disease Intervention/treatment Phase
Smoking Cessation Genetic Predisposition Drug: Varenicline Tartrate or bupropion Not Applicable

Detailed Description:

The patients will be invited to take part in the study collection genetic´s materials in order to determinate the frequency of CHRNA4 AND CYP2B6.

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The Patients will be randomized in two arms. 150 will be treated in the pharmacogenetic arm and 150 in the varenicline arm ( control ).
Masking: Double (Participant, Investigator)
Masking Description:

The patients will be totally blinded to know which arms will be used in the treatment.

The investigator who makes clinical visits of the protocol do not have access to randomizing list, therefore they are blinded for the use of varenicline indicated, but not for bupropion use.

Primary Purpose: Treatment
Official Title: Evaluation of the Efficacy of the Use of Genetic Markers in the Choice of the Pharmacological Treatment of Smoking
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Smoking

Arm Intervention/treatment
No Intervention: 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.
Active Comparator: 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.

Drug: 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 Name: Varenicline Tartrate and bupropion




Primary Outcome Measures :
  1. Abstinence rate at the end of study [ Time Frame: Between week 8 until week 12 ]
    Continuous abstinence Rate confirmed througth carbon monoxide concentration in exhalated air


Secondary Outcome Measures :
  1. Abstinence rate at week 4 [ Time Frame: At week 4 ]
    Point prevalence


Other Outcome Measures:
  1. Safety evaluation [ Time Frame: week 0 until week 12 ]
    Adverse events according to subjects´ self-reported



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • smoking who wants to quit smoking, stable clinic diseases, depression or anxiety disorder stable for more than 3 months

Exclusion Criteria:

  • contra indication for varenicline and or bupropion
  • unstable psychiatric disorders.
  • In the treatment of neoplastic diseases.
  • Limitation to attend the medical visits

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): NCT03362099


Contacts
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Contact: Jaqueline R Scholz, MD, Phd 55112661.5592 jaquelineincor@yahoo.com.br
Contact: Patricia v Gaya, MD 551126615698 gaya_00@hotmail.com

Locations
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Brazil
Ambulatório de Tratamento Tabagismo - Incor HCFMUSP Recruiting
São Paulo, Brazil, 05403000
Sponsors and Collaborators
University of Sao Paulo General Hospital
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
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Principal Investigator: Jaqueline R Scholz, MD.Phd Heart Institute - University of São Paulo - Braziil

Additional Information:
Publications:
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Responsible Party: Jaqueline Scholz, Principal Investigator, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT03362099     History of Changes
Other Study ID Numbers: 6013381600000068
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Jaqueline Scholz, University of Sao Paulo General Hospital:
varenicline
bupropion

Additional relevant MeSH terms:
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Varenicline
Disease Susceptibility
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes
Bupropion
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Agents
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors