An observational study in Smoking Cessation, Smoking Cessation Intervention and Nicotine Addiction, sponsored by University of Cyprus. Recruiting at 1 site in Cyprus. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-06-25.
Sponsored by University of Cyprus · Observational
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.
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.
1,581 studies on the registry are indexed under Smoking Cessation; 198 are open to participants now.
This study's planned enrollment of 200 is close to the median of 216 across 116 observational studies indexed under Smoking Cessation.
Browse Smoking Cessation studies →University of Cyprus is the lead sponsor of 28 studies on the registry; 10 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The study population will consist of adult daily cigarette smokers recruited from communities across Cyprus who are able to attend study visits at the research facilities in Nicosia. Recruitment will leverage multiple avenues including primary care clinics, community outreach, word-of-mouth referrals, and smoking cessation services throughout the island. The goal is to enroll approximately 200 eligible participants, with equal representation of men and women, from both urban and rural areas of Cyprus. No other specific characteristics beyond meeting eligibility criteria are used to identify or restrict the source population.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants who achieve biochemically-verified smoking abstinence for at least 6 months following a cessation attempt aided by a computerized intervention program.
Behavioral: Flexiquit Smoking Cessation Intervention
Participants who do not achieve abstinence and relapse to smoking following the cessation attempt.
Behavioral: Flexiquit Smoking Cessation Intervention
Participants will enter a 6-week (once weekly) self-delivered computerized intervention program called Flexiquit. Developed and validated by Clinical Psychologists of the Department of Psychology at the University of Cyprus, Flexiquit is an avatar-led app designed to support smoking cessation. It aims to assist with abstinence and monitor participants' progress through personalized modules and assessments.
Novel druggable gene targets for smoking cessation
Genes encoding druggable proteins (targets of approved drugs or clinical candidates) whose genetically predicted expression levels are found to be causally associated with smoking cessation outcomes using Mendelian randomization approaches.
Time frame: Upon completion of Mendelian randomization analysis
Association between methylation of candidate genes and nicotine dependence scores
Difference in methylation levels of top genes between participants with high vs. low scores on the Fagerström Test for Nicotine Dependence.
Time frame: Baseline
Association between DNA methylation of candidate drug target genes and motivation to quit smoking scores
Difference in methylation levels of the top candidate drug target genes between participants with high vs. low scores on a validated motivation to quit smoking questionnaire.
Time frame: 3 and 6 months post nicotine cessation
Association between methylation and smoking relapse vulnerability
Difference in methylation of top genes between cases achieving 6+ month abstinence vs. controls who relapsed to smoking.
Time frame: 3 and 6 months post nicotine cessation
Gender differences in methylation associations
Differences between males and females in the associations between methylation of candidate genes and the motivation, dependence and relapse outcomes.
Time frame: 3 and 6 months post nicotine cessation
Plan to share: No
Started Nov 2023 (actual). Primary completion is estimated for Oct 2025, 23 months after the start.
Of 42 non-industry observational studies under Smoking Cessation, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 90. This study's planned 23 months is below that.
Counting every sponsor, half of 47 studies reached it within 31 months; a quarter within 17 and three quarters within 90.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Cyprus