Unraveling the Genetic Basis of Nicotine Addiction for Novel Therapeutic Strategies

Last updated: June 23, 2024
Sponsor: University of Cyprus
Overall Status: Active - Recruiting

Phase

N/A

Condition

Tobacco Use Disorder

Substance Abuse

Smoking Cessation

Treatment

Flexiquit Smoking Cessation Intervention

Clinical Study ID

NCT06471387
Onisilos2023
Onisilos-co-fund182
  • Ages 18-60
  • All Genders

Study Summary

This case-control study aims to investigate the genetic and molecular bases of nicotine addiction to identify potential therapeutic targets. The project will involve drug repurposing using Mendelian Randomization, a smoking cessation intervention, and the analysis of methylation status in participants undergoing nicotine withdrawal.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Adults aged 18-60 years old

  • Current daily cigarette smoker

  • Able to understand study procedures and provide informed consent

  • For females, non-pregnant and non-lactating

Exclusion

Exclusion Criteria:

  • Presence of significant uncontrolled medical conditions (e.g. cardiovasculardisease, respiratory disorders, cancer) that could affect smoking behaviors or studyparticipation

  • Presence of major uncontrolled psychiatric disorders (e.g. schizophrenia, bipolardisorder, severe depression)

  • Current substance use disorder (except nicotine dependence)

  • Taking medications that could significantly interfere with study objectives (e.g.medications for smoking cessation)

  • Significant cognitive impairment that precludes ability to complete study procedures

Study Design

Total Participants: 200
Treatment Group(s): 1
Primary Treatment: Flexiquit Smoking Cessation Intervention
Phase:
Study Start date:
November 01, 2023
Estimated Completion Date:
October 31, 2025

Study Description

Cigarette smoking remains the largest preventable risk factor for chronic diseases and premature mortality worldwide. While several medications have been approved to aid smoking cessation, most individuals relapse following an initial period of abstinence, with only around 15% achieving long-term abstinence beyond 6-12 months. This highlights a critical need to identify novel drug targets and develop more effective pharmacotherapies to treat nicotine addiction and maintain long-term smoking abstinence.

The proposed case-control study aims to leverage an interdisciplinary approach combining genetic epidemiology and molecular biology to: 1) Identify potential novel druggable targets for smoking cessation using a drug repurposing Mendelian randomization (MR) strategy, and 2) Assess whether epigenetic modifications (DNA methylation) of the identified drug target genes are associated with motivation to quit smoking, nicotine dependence severity, and vulnerability to smoking relapse following a cessation attempt.

Specifically, NicoGen study utilizes large-scale genomic datasets of expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) to identify genetic variants that influence expression/levels of genes encoding druggable proteins (targets of approved drugs/clinical candidates). MR analyses will then determine if genetically-predicted expression of these genes is causally related to smoking cessation outcomes.

Additionally, 200 current cigarette smokers (100 men, 100 women) will be recruited prior to smoking cessation for collection of biofluids for DNA extraction.

The methylation levels of the top candidate drug target genes identified in will be assessed and compared between: 1) Cases who achieve ≥6 month abstinence vs. relapsed controls, 2) High vs. low motivation to quit groups, and 3) High vs. low nicotine dependence groups. This allows identification of epigenetic biomarkers predictive of cessation outcomes.

Additionally, potential gender differences in the associations between gene methylation, motivation, dependence and relapse vulnerability will be explored to identify gender-specific drug targets.

Connect with a study center

  • Center for Applied Neuroscience (CAN)

    Nicosia, 2100
    Cyprus

    Active - Recruiting

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