Impact of a Gene Test for Susceptibility to Lung Cancer in Smokers
Professor RP Young (Associate Professor of Medicine and Molecular Medicine, School of Biological Sciences, University of Auckland) and his team have developed a reliable genetic test "Respiragene" based on 20 single nucleotide polymorphisms that can be used (together with details of personal and family history) to calculate a smoker's lifetime risk of developing lung cancer. The expectation is that whatever the score (estimated lifetime risk will vary from 5% to 50%) the result will counter "optimism bias" of the smoker and encourage smoking cessation and this assumption is supported by previous research on similar tests and smoking cessation. The investigators plan to recruit two groups of subjects for smoking cessation but only one group will have the Respiragene test. Eight weekly smoking cessation sessions will be carried out at a Surrey primary care medical centre and will follow the usual format for National Health Service smoking cessation clinics using Champix (varenicline), counselling and the carbon monoxide breath meter but with added: evaluation questionnaires, fagerstrom nicotine addiction score, salivary cotinine (metabolite of nicotine) test. The main outcome measures will be estimation of smoking cessation at 4 weeks and six months after the completion of the seven smoking cessation sessions. Successful smoking cessation has to be confirmed by negative salivary cotinine at 4 weeks and six months and questionnaires will be used to estimate the influence of the Respiragene test compared with standard procedures such as counselling and the carbon monoxide breath readings.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
|Official Title:||A Protocol for an Randomised Controlled Trial of Smoking Cessation Success Rate With or Without a Genetic Test, "Respiragene", to Assess Lung Cancer Risk - an Exploratory Study|
- Number of subjects versus controls who are non-smokers at 4 weeks and six months after completion of smoking cessation clinic [ Time Frame: Nine months (from recruitment to completion) ] [ Designated as safety issue: No ]Subjects and controls will be reassessed at 4 weeks and six months after the last smoking cessation session to determine how many have genuinely stopped smoking. This will be confirmed at the six month follow up by measuring salivary cotinine to reveal any subjects who are being untruthful. The difference between quit rates in subjects and controls can then be calculated.
- Questionnaires to assess efficacy of Repiragene test as a motivator compared with other smoking cessation aids and motivators [ Time Frame: Nine months (from recruitemnt to completion) ] [ Designated as safety issue: No ]All subjects will be asked to complete questionnaires (with assistance as needed) to assess the perceived value of the Respiragene test compared with other motivators (such as the price of cigarettes, family pressure etc.) and other motivational triggers used in the clinic (salivary cotinine, spirometry results etc.)
|Study Start Date:||September 2011|
|Study Completion Date:||March 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
No Intervention: Control group
The control group will have a standard NHS cessation clinic experience
Experimental: Respiragene test and risk score
Subjects will have a buccal swab taken at first attendance for a 12 gene test of SNP variants associated with risk of lung cancer. From the genetic data and clinical data (any history of COPD, family history of lung cancer in a first degree relative and age) a risk score is calculated from which a lifetime risk of lung cancer if the subject continues to smoke can be calculated. This is expected to be a powerful motivator to encourage smoking cessation.
Genetic: Respiragene test and risk score
This 12 gene test used with other data (family history, age and spirometry result) to calculate lifetime risk of lung cancer in smokers who do not quit smoking. This intervention is expected to be a motivator to quit.
Other Name: Respiragene test, Lab 21, Cambridge
Despite the 5-10% probability of lung cancer in smokers, 50% do not believe they are at significantly increased risk Despite this, over 80% of smokers would like to know their personal risk of lung cancer. RP Young, a clinician at University of Auckland, has show a three way link between biomarkers for COPD, a set of 20 single nucleotide polymorphisms (SNPs) and lung cancer. He has demonstrated a strong correlation between a risk score (derived from family history of cancer, the 20 SNPs & clinical COPD) and the development of lung cancers whereas healthy smokers (who had not developed lung cancer) matched for age, gender and lifetime smoking habits had a relatively low risk score (n=446 lung cancer subjects, 484 healthy current smokers. The odds ratio for lung cancer risk varied from 0.2-3.2 depending on the genetic risk (p<0.001). The Auckland lung cancer risk score has a 90% sensitivity for a score of >4. The validity of 20 SNP gene test has also been confirmed in populations in Barcelona, Spain and Liverpool, United Kingdom. The test has been given the trade name "Respiragene".
Small uncontrolled trials of use of Respiragene in smoking cessation clinics in New Zealand and USA show an improvement in smoking cessation at six months after a Respiragene intervention with quit rates of 30-35%. The trial hypothesis is that smokers who have the Respiragene test and a full explanation of their risk score will have a better quit rate at 4 weeks and at six months (after completion of their eight weekly smoking cessation clinic sessions) than controls. Smoking cessation at the six month follow up will bw confirmed by testing for salivary cotinine. Based on data from Young's small trial, we also hypothesise that this uplift of quit rate will be seen for subjects with both high risk scores and average risk scores (there is no low risk category for smokers). These hypotheses are the basis of the primary end points.
The investigators will also be administering the same questionnaire to each subject and control twice, at 4 weeks and six months (after the smoking cessation course) that is primarily designed to evaluate the impact of the Respiragene test in relation to other influences:
- other components of the smoking cessation clinic sessions (salivary cotinine testing, carbon monoxide breath analyser, general clinic help and advice, clinic fact sheets)
- general environmental factors (cost of cigarettes, family pressure, work regulations, doctor's advice)
The results will be analysed using Statistical Package for the Social Sciences (SPSS) Statistics 17.0 computer programme.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01176383
|The Integrated Care Partnership The Old Cottage Hospital Alexandra Road,|
|Epsom, Surrey, United Kingdom, KT17 4BL|
|Principal Investigator:||John Nichols, MB ChB||Surrey Primary Care Research Unit|