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

Primary Purpose

Smoking Cessation, Genetic Predisposition

Status
Completed
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Varenicline Tartrate or bupropion
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Smoking Cessation focused on measuring varenicline, bupropion

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Ambulatório de Tratamento Tabagismo - Incor HCFMUSP

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Group Varenicline

Group Genetic

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Bupropion favorable genetic marker
Abstinence Rate confirmed througth carbon monoxide concentration in exhalated air in favorable bupropion smokers vs control arm with varenicline
Varenicline favorable genetic marker
abstinence rate confirmed through carbon monoxide concentration in exhalated air in favorable varenicline genetic marker vs unfavorable varenicline genetic marker

Secondary Outcome Measures

Abstinence rate at week 12
Evaluation of add therapy for quitting smoking considering favorable and unfavaroble genetics markers

Full Information

First Posted
November 16, 2017
Last Updated
December 16, 2022
Sponsor
University of Sao Paulo General Hospital
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT03362099
Brief Title
Efficacy of the Use of Genetic Markers in the Choice of the Pharmacological Treatment of Smoking (GENTSMOKING)
Acronym
GENTSMOKING
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.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
November 1, 2016 (Actual)
Primary Completion Date
April 15, 2022 (Actual)
Study Completion Date
April 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo General Hospital
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoking Cessation, Genetic Predisposition
Keywords
varenicline, bupropion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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
ParticipantCare Provider
Masking Description
The patients are blinded when they use varenicline. The care provider 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.
Allocation
Randomized
Enrollment
361 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group Varenicline
Arm Type
No Intervention
Arm Description
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.
Arm Title
Group Genetic
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Varenicline Tartrate or bupropion
Other Intervention Name(s)
Varenicline Tartrate and bupropion
Intervention Description
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.
Primary Outcome Measure Information:
Title
Bupropion favorable genetic marker
Description
Abstinence Rate confirmed througth carbon monoxide concentration in exhalated air in favorable bupropion smokers vs control arm with varenicline
Time Frame
week 4 -
Title
Varenicline favorable genetic marker
Description
abstinence rate confirmed through carbon monoxide concentration in exhalated air in favorable varenicline genetic marker vs unfavorable varenicline genetic marker
Time Frame
week 4
Secondary Outcome Measure Information:
Title
Abstinence rate at week 12
Description
Evaluation of add therapy for quitting smoking considering favorable and unfavaroble genetics markers
Time Frame
At week 12
Other Pre-specified Outcome Measures:
Title
Safety evaluation
Description
Adverse events according to subjects self-reported
Time Frame
week 0 until week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaqueline R Scholz, MD.Phd
Organizational Affiliation
Heart Institute - University of São Paulo - Braziil
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ambulatório de Tratamento Tabagismo - Incor HCFMUSP
City
São Paulo
ZIP/Postal Code
05403000
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26153084
Citation
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.
Results Reference
background
PubMed Identifier
25774163
Citation
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.
Results Reference
background
Links:
URL
https://link.springer.com/article/10.1007/s00228-015-1896-x?no-access=true#citeas
Description
CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy
URL
https://www.frontiersin.org/articles/10.3389/fgene.2015.00046/full
Description
CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy

Learn more about this trial

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

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