Smoking CessationNicoGenNCT06471387
Unraveling the Genetic Basis of Nicotine Addiction for Novel Therapeutic Strategies
An observational study of Smoking Cessation and Smoking Cessation Intervention, run by University of Cyprus at 1 site in Cyprus.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Smoking Cessation, Smoking Cessation Intervention, Nicotine Addiction
- What is being tested?
- Flexiquit Smoking Cessation Intervention
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 200 participants
- Where
- 1 siteCyprus
- Study dates
- 1 Nov 2023to 31 Oct 2025
- Phase
- Observational
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: 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.
Who may be able to join
- 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
Who cannot join
- Presence of significant uncontrolled medical conditions (e.g. cardiovascular disease, respiratory disorders, cancer) that could affect smoking behaviors or study participation
- Presence of major uncontrolled psychiatric disorders (e.g. schizophrenia, bipolar disorder, 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
Trial locations and contacts
1 site in 1 country.
Cyprus1 site, 1 recruiting
- Recruiting
Center for Applied Neuroscience (CAN)
Nicosia, 2100
Andrea Georgiou, Ph.D., georgiou.andrea@ucy.ac.cy
About this study
Official title: Exploring the Genetic and Molecular Underpinning of Nicotine Addiction for the Development of New Therapeutic Strategies
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.
Read the detailed 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.
- Conditions
- Smoking Cessation, Smoking Cessation Intervention, Nicotine Addiction, Epigenetics, Molecular Biology, Genetic Epidemiology
- Being tested
- Flexiquit Smoking Cessation Intervention
- Keywords
- Nicotine Addiction, Smoking Cessation, Mendelian Randomization, Methylation, Genetic Epidemiology, Drug Repurposing, Epigenetic Biomarkers
- Medical subject headings
- Smoking Cessation, Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flexiquit Smoking Cessation InterventionBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Abstainers | Participants who achieve biochemically-verified smoking abstinence for at least 6 months following a cessation attempt aided by a computerized intervention program. Receives: Behavioral: Flexiquit Smoking Cessation Intervention | |
| Relapsers | Participants who do not achieve abstinence and relapse to smoking following the cessation attempt. Receives: Behavioral: Flexiquit Smoking Cessation Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 3 and 6 months post nicotine cessation
Secondary outcomes (1)
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.
Measured: 3 and 6 months post nicotine cessation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2024
- Study start1 Nov 2023
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cyprus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Panos Zanos, University of Cyprus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06471387
- Sponsor's protocol ID
- Onisilos2023
- Other IDs
- Onisilos-co-fund182
- Acronym
- NicoGen
- Status last verified
- Jun 2024
- First submitted
- 18 Jun 2024
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Karekla M, Savvides SN, Gloster A. An Avatar-Led Intervention Promotes Smoking Cessation in Young Adults: A Pilot Randomized Clinical Trial. Ann Behav Med. 2020 Oct 1;54(10):747-760. doi: 10.1093/abm/kaaa013.
PubMed 32383736
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Genetic and Molecular Underpinning of Nicotine Addiction for the Development of New Therapeutic Strategies
- ClinicalTrials.gov ID
- NCT06471387
- Acronym / sponsor ID
- NicoGen / Onisilos2023
- Conditions
- Smoking Cessation, Smoking Cessation Intervention, Nicotine Addiction, Epigenetics, Molecular Biology, Genetic Epidemiology
- Keywords
- Nicotine Addiction, Smoking Cessation, Mendelian Randomization, Methylation, Genetic Epidemiology, Drug Repurposing, Epigenetic Biomarkers
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of CyprusUniversity, hospital or other
- Study start
- 1 Nov 2023 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Oct 2025 (estimated)
- First posted
- 24 Jun 2024 (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.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Abstainers | – | Behavioral: Flexiquit Smoking Cessation InterventionParticipants who achieve biochemically-verified smoking abstinence for at least 6 months following a cessation attempt aided by a computerized intervention program. |
| Relapsers | – | Behavioral: Flexiquit Smoking Cessation InterventionParticipants who do not achieve abstinence and relapse to smoking following the cessation attempt. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- Presence of significant uncontrolled medical conditions (e.g. cardiovascular disease, respiratory disorders, cancer) that could affect smoking behaviors or study participation
- Presence of major uncontrolled psychiatric disorders (e.g. schizophrenia, bipolar disorder, 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
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 |
|---|---|---|
| Flexiquit Smoking Cessation InterventionParticipants 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. | Behavioural | Abstainers, Relapsers |
Primary outcome
Novel druggable gene targets for smoking cessation
Time frame: Upon completion of Mendelian randomization analysis
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.
Association between methylation of candidate genes and nicotine dependence scores
Time frame: Baseline
Difference in methylation levels of top genes between participants with high vs. low scores on the Fagerström Test for Nicotine Dependence.
Association between DNA methylation of candidate drug target genes and motivation to quit smoking scores
Time frame: 3 and 6 months post nicotine cessation
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.
Association between methylation and smoking relapse vulnerability
Time frame: 3 and 6 months post nicotine cessation
Difference in methylation of top genes between cases achieving 6+ month abstinence vs. controls who relapsed to smoking.
1 secondary outcome
Gender differences in methylation associations
Time frame: 3 and 6 months post nicotine cessation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
- Background: PubMed 32383736Karekla M, Savvides SN, Gloster A. An Avatar-Led Intervention Promotes Smoking Cessation in Young Adults: A Pilot Randomized Clinical Trial. Ann Behav Med. 2020 Oct 1;54(10):747-760. doi: 10.1093/abm/kaaa013.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Smoking Cessation and Smoking Cessation Intervention, run by University of Cyprus at 1 site in Cyprus.
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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 25 Jun 2024. 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 Cyprus. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrea N Georgiou, Ph.D. ((+357)-22893372, georgiou.andrea@ucy.a.cy), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Novel druggable gene targets for smoking cessation (time frame: Upon completion of Mendelian randomization analysis). The study lists 4 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 NCT06471387, which also lists 1 linked publication.
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 25 Jun 2024.