Smoking CessationPhase 4GENTSMOKINGNCT03362099
Efficacy of the Use of Genetic Markers in the Choice of the Pharmacological Treatment of Smoking (GENTSMOKING)
A Phase 4 study testing Varenicline Tartrate or bupropion in people with Smoking Cessation and Genetic Predisposition, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking Cessation, Genetic Predisposition
- What is being tested?
- Varenicline Tartrate or bupropion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 361 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Nov 2016to 15 Apr 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- smoking who wants to quit smoking, stable clinic diseases, depression or anxiety disorder stable for more than 3 months
Who cannot join
- contra indication for varenicline and or bupropion
- unstable psychiatric disorders.
- In the treatment of neoplastic diseases.
- Limitation to attend the medical visits
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Ambulatório de Tratamento Tabagismo - Incor HCFMUSP
São Paulo, 05403000
About this study
Official title: Efficacy of Genetic Markers in Choosing Pharmacological Treatment for Smoking Cessation With Bupropion and Varenicline and Its Implications for Combining Drugs: Randomized Control Study.
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.
Read more
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.
Read the 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.
- Conditions
- Smoking Cessation, Genetic Predisposition
- Being tested
- Varenicline Tartrate or bupropion
- Keywords
- varenicline, bupropion
- Medical subject headings
- Smoking Cessation, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Varenicline Tartrate or bupropionDrug
Also called Varenicline Tartrate and 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.
| Study group | Role | What they receive |
|---|---|---|
| Group Varenicline | No intervention | 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. |
| Group Genetic | Active comparator | 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. Receives: Drug: Varenicline Tartrate or bupropion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bupropion favorable genetic marker
Abstinence Rate confirmed througth carbon monoxide concentration in exhalated air in favorable bupropion smokers vs control arm with varenicline
Measured: week 4 -
Varenicline favorable genetic marker
abstinence rate confirmed through carbon monoxide concentration in exhalated air in favorable varenicline genetic marker vs unfavorable varenicline genetic marker
Measured: week 4
Secondary outcomes (1)
Abstinence rate at week 12
Evaluation of add therapy for quitting smoking considering favorable and unfavaroble genetics markers
Measured: At week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2017
- Study start1 Nov 2016
- Primary completion15 Apr 2022
- Study completion15 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The Patients will be randomized in two arms. 200 will be treated in the pharmacogenetic arm and 200 in the varenicline arm ( control ).
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 361 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Principal investigator, Jaqueline Scholz, University of Sao Paulo General Hospital
- Investigators
- Jaqueline R Scholz, MD.Phd, Principal investigator, Heart Institute - University of São Paulo - Braziil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03362099
- Sponsor's protocol ID
- 6013381600000068
- Acronym
- GENTSMOKING
- Status last verified
- Dec 2022
- First submitted
- 16 Nov 2017
- Last updated
- 21 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26153084Rocha 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.
PubMed 25774163Gaya 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.
PubMed 38756738Gaya 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.
PubMed 38628555
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Genetic Markers in Choosing Pharmacological Treatment for Smoking Cessation With Bupropion and Varenicline and Its Implications for Combining Drugs: Randomized Control Study.
- ClinicalTrials.gov ID
- NCT03362099
- Acronym / sponsor ID
- GENTSMOKING / 6013381600000068
- Conditions
- Smoking Cessation, Genetic Predisposition
- Keywords
- varenicline, bupropion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 361 participants (actual)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 15 Apr 2022 (actual)
- Study completion
- 15 Apr 2022 (actual)
- First posted
- 5 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- The Patients will be randomized in two arms. 200 will be treated in the pharmacogenetic arm and 200 in the varenicline arm ( control ).
| Arm | Type | Receives |
|---|---|---|
| Group Varenicline | No intervention | –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. |
| Group Genetic | Active comparator | Drug: Varenicline Tartrate or bupropionThe 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- smoking who wants to quit smoking, stable clinic diseases, depression or anxiety disorder stable for more than 3 months
Key exclusion criteria (4 listed)
- contra indication for varenicline and or bupropion
- unstable psychiatric disorders.
- In the treatment of neoplastic diseases.
- Limitation to attend the medical visits
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Varenicline Tartrate or bupropionAlso: Varenicline Tartrate and bupropionthe 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. | Drug | Group Genetic |
Primary outcome
Bupropion favorable genetic marker
Time frame: week 4 -
Abstinence Rate confirmed througth carbon monoxide concentration in exhalated air in favorable bupropion smokers vs control arm with varenicline
Varenicline favorable genetic marker
Time frame: week 4
abstinence rate confirmed through carbon monoxide concentration in exhalated air in favorable varenicline genetic marker vs unfavorable varenicline genetic marker
1 secondary outcome
Abstinence rate at week 12
Time frame: At week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
- Background: PubMed 26153084Tomaz 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.
- Background: PubMed 25774163Rocha 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.
- Derived from this study: PubMed 38756738Gaya 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.
- Derived from this study: PubMed 38628555Gaya 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.
- CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapyLink provided by the sponsor.
- CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaqueline R Scholz, MD.Phd principal investigator
Heart Institute - University of São Paulo - Braziil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Varenicline Tartrate or bupropion in people with Smoking Cessation and Genetic Predisposition, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bupropion favorable genetic marker (time frame: week 4 -). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03362099, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2022.