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

NCT03362099 | Completed Phase 4 DMC

• 1 other identifier: 6013381600000068
• Study Type: interventional
• Target: 361
• Locations: 1 country
• Sites: 1

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.

Conditions

Smoking Cessation; Genetic Predisposition

Keywords

varenicline; bupropion

Outcome Measures

Primary Outcomes (2)

• Bupropion favorable genetic marker

  Abstinence Rate confirmed througth carbon monoxide concentration in exhalated air in favorable bupropion smokers vs control arm with varenicline

  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

  week 4

Secondary Outcomes (1)

• Abstinence rate at week 12

  At week 12

Other Outcomes (1)

• Safety evaluation

  week 0 until week 12

Study Arms (2)

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.

Drug: Varenicline Tartrate or bupropion

Interventions

Varenicline Tartrate or bupropion DRUG

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.

Also known as: Varenicline Tartrate and bupropion

Group Genetic

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (1)

Ambulatório de Tratamento Tabagismo - Incor HCFMUSP

São Paulo, 05403000, Brazil

Location

Related Publications (4)

• 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.

  PMID: 26153084 BACKGROUND

• 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.

  PMID: 25774163 BACKGROUND

• 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.

  PMID: 38756738 DERIVED

• 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.

  PMID: 38628555 DERIVED

Related Links

• CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy
• CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy

MeSH Terms

Conditions

Smoking Cessation; Genetic Predisposition to Disease

Interventions

Varenicline; Bupropion

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Propiophenones; Ketones; Organic Chemicals

Study Officials

• Jaqueline R Scholz, MD.Phd

  Heart Institute - University of São Paulo - Braziil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The Patients will be randomized in two arms. 200 will be treated in the pharmacogenetic arm and 200 in the varenicline arm ( control ).

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: December 5, 2017
• Study Start: November 1, 2016
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: December 21, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)