Impact of a Gene Test for Susceptibility to Lung Cancer in Smokers

This study has been completed.
Sponsor:
Collaborators:
University of Surrey
Lab 21, Cambridge
NHS Research and Development
Information provided by (Responsible Party):
John Nichols, University of Surrey
ClinicalTrials.gov Identifier:
NCT01176383
First received: August 3, 2010
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Smoking Cessation
Genetic: Respiragene test and risk score

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Sussex NHS Research Consortium:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.)


Enrollment: 67
Study Start Date: September 2011
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 20-70 years
  • Smoking more than 10 cigarettes daily

Exclusion Criteria:

  • Aged under 20 years or over 70 years
  • Smoking less than 10 cigarettes daily
  • History of major depression and other psychiatric conditions, dementias and serious or terminal illness (cancers etc.).
  • Patients on warfarin would be excluded due to interactions between warfarin and varenicline as varenicline will be used as the modern treatment of choice for smoking cessation.

Patients who did not wish to have a genetic test would be referred to the practice nurse for smoking cessation.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01176383

Locations
United Kingdom
The Integrated Care Partnership The Old Cottage Hospital Alexandra Road,
Epsom, Surrey, United Kingdom, KT17 4BL
Sponsors and Collaborators
Sussex NHS Research Consortium
University of Surrey
Lab 21, Cambridge
NHS Research and Development
Investigators
Principal Investigator: John Nichols, MB ChB Surrey Primary Care Research Unit
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John Nichols, Visiting Research fellow, University of Surrey
ClinicalTrials.gov Identifier: NCT01176383     History of Changes
Other Study ID Numbers: SPCRU1
Study First Received: August 3, 2010
Last Updated: May 13, 2014
Health Authority: United Kingdom: National Health Service

Keywords provided by Sussex NHS Research Consortium:
Nicotine addiction
Behaviour
Gene test
Lung cancer
Lifetime risk of lung cancer in smokers

Additional relevant MeSH terms:
Lung Neoplasms
Smoking
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Habits

ClinicalTrials.gov processed this record on July 23, 2014