Unraveling the Genetic Basis of Nicotine Addiction for Novel Therapeutic Strategies

NCT06471387 | Recruiting

• 2 other identifiers: Onisilos2023Onisilos-co-fund182
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  3 and 6 months post nicotine cessation

Secondary Outcomes (1)

• Gender differences in methylation associations

  3 and 6 months post nicotine cessation

Study Arms (2)

Abstainers

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

Relapsers

Participants who do not achieve abstinence and relapse to smoking following the cessation attempt.

Behavioral: Flexiquit Smoking Cessation Intervention

Interventions

Flexiquit Smoking Cessation Intervention BEHAVIORAL

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.

Abstainers; Relapsers

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cyprus: lead

Study Sites (1)

Center for Applied Neuroscience (CAN)

Nicosia, 2100, Cyprus

RECRUITING

Related Publications (1)

• 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.

  PMID: 32383736 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and saliva

MeSH Terms

Conditions

Smoking Cessation; Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Central Study Contacts

Andrea N Georgiou, Ph.D.

CONTACT

(+357)-22893372; georgiou.andrea@ucy.a.cy

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: June 24, 2024
• Study Start: November 1, 2023
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CY (1)