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

May 13, 2014 updated by: John Nichols, Sussex NHS Research Consortium

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

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 Overview

Status

Completed

Conditions

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.

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Surrey
      • Epsom, Surrey, United Kingdom, KT17 4BL
        • The Integrated Care Partnership The Old Cottage Hospital Alexandra Road,

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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 Names:
  • Respiragene test, Lab 21, Cambridge

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
Nine months (from recruitment to completion)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.)
Nine months (from recruitemnt to completion)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: John Nichols, MB ChB, Surrey Primary Care Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

August 3, 2010

First Submitted That Met QC Criteria

August 5, 2010

First Posted (Estimate)

August 6, 2010

Study Record Updates

Last Update Posted (Estimate)

May 14, 2014

Last Update Submitted That Met QC Criteria

May 13, 2014

Last Verified

May 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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