Clinical trial NCT01186016: Developing Genetic Education for Smoking Cessation
Official title: Developing Genetic Education for Smoking Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Smoking
Keywords: Genetic Education
Smoking Cessation
Quitting Smoking
Standard Smoking Cessation Program
Genetic Education for Smoking Cessation
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2010-08-20
Enrollment: 103
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will test the effects of an educational program about genetics and smoking on smokers' thoughts, feelings, and behaviors before and after participating in smoking cessation treatment. This includes describing participants' knowledge about genetics and smoking, their use of strategies to stop smoking, and experiences when quitting smoking. This study will determine how smokers respond to information about genetics and smoking in anticipation of using genetic information to individualize pharmacological therapy for smoking cessation.

Two groups will participate in this study. The experimental group will participate in two educational sessions about genetics and smoking. The control group will participate in two educational sessions about nutrition. Both the experimental and control groups will participate in a standard, group smoking cessation program with 6 weeks of over-the-counter (OTC) transdermal nicotine replacement therapy. Assignment to either of the two groups is random.

The primary specific aim is to compare the effects of the experimental group to the attention control group on smoking-related mental representations, appraisals, behaviors, and affective responses over time. The secondary aim is to explore whether personality characteristics (trait negative affectivity and curiosity) and educational level moderate the effects of the genetic educational program on smoking-related mental representations, appraisals, behaviors, and affective responses. The hypotheses of the study are as follows:

1. When compared to the attention control group, the experimental group will demonstrate:

   * Smoking-Related Mental Representations:
   * Greater knowledge of genetic contributions to smoking
   * Greater endorsement of genetic contributions to smoking
   * More positive attitudes towards NRT
   * Increased abstainer and decreased smoker self-schemas
   * Smoking-Related Appraisal: greater perceived risk for genetic predispositions to smoking
   * Smoking-Related Behaviors: greater interest in genotyping.
2. When compared to the attention control group, the experimental group will differ in:

   * Smoking-Related Appraisals: self-efficacy for cessation and abstinence
   * Smoking-Related Behaviors: number of quit attempts, abstinence, nicotine dependence
   * Affective Responses: negative affect and intrusive/avoidant thoughts

Detailed description: Background. Reducing cigarette smoking among adults is a major public health objective. Although the target prevalence for adult smoking is \< 12% by 2010 (DHHS 2000), current estimates indicate that 20.8%, or 45.3 million adults, currently smoke (CDC, 2007). An estimated 44.2% of smokers tried to quit at least one day in the last 12 months (CDC, 2007), yet \<10% of smokers who try to quit remain abstinent (Benowitz, 2008). Even with intensive treatment, only 11-20% of smokers are abstinent for 6 months (Sutherland, 2003). Smoking also results in an enormous economic burden, with health-care and lost productivity costs totaling approximately $167 billion per year (CDC, 2008). A limitation of current treatment guidelines is a lack of specificity for individual smokers. Completion of the sequencing of the human genome and the current focus on genomics (Collins, Green, Guttmacher, \& Guyer, 2003) provides an unprecedented opportunity to study the biobehavioral factors influencing smoking. This research will contribute to individualized treatment by providing a better understanding of the effects of genetic, psychological, and environmental factors and their interaction on smoking initiation, maintenance, cessation, and relapse (Lerman, Schnoll \& Munafo, 2007; Morgan et al., 2003; Swan et al., 2003). Both candidate gene studies to identify specific genes that affect smoking and pharmacogenomic studies that investigate the effects of selected genes on treatment response contribute to a growing body of knowledge about genetic influences on smoking. The anticipated outcome of these studies will be the ability to individualize type, dose, and duration of treatment based on smokers' genotypes (Lerman, Schnoll \& Munafo). Ultimately, the long-term goal of this research is to decrease relapse and promote sustained abstinence.

The Genetic Education and Smoking Model provides a framework for investigating variables that potentially influence the ways smokers respond to information about: (a) genetic contributions to smoking and (b) the potential for genetically-informed cessation treatment. Based on social-cognitive theory and the Common Sense Model (CSM)(Cervone, 2004; Brownlee, Leventhal, \& Leventhal, 2000), the Genetic Education and Smoking Model proposes that genetic education will influence smokers' mental representations and appraisals about genetics and smoking in addition to their smoking-related behaviors and affective responses.

As genetically-informed cessation treatment becomes a part of research and clinical care, smokers will need a degree of genetic literacy to make informed decisions (McInerney, 2002; Shields, Lerman, \& Sullivan, 2004). There is a growing body of scientific knowledge to guide an educational program about genetic contributions to smoking and the potential for genetically-informed cessation treatment. Epidemiologic twin studies consistently support a genetic cause for smoking, with an estimated 56% of the variance for smoking initiation and 67% of progression to nicotine dependence due to additive genetic effects (Sullivan and Kendler, 1999). Findings from several genome-wide scans using linkage analysis have identified chromosomes 1, 2, 4, 5, 6, 9, 10, 11, 14, 17, 18, and 21 as containing possible susceptibility loci for smoking-related genes (Li,Cheng, Ma, \& Swan, 2003; Li, Ma, \& Beuten, 2004). Several candidate-genes for smoking heritability have been identified, including nicotinic acetylcholine receptors (nAChRs), dopamine receptor (DRD2 and DRD4) and transporter (SLC6A3) genes, the catechol-o-methyl-transferase (COMT) gene, the mu opioid receptor (OPRM1) gene, and the serotonin transporter (5-HTT) gene (Lerman, Schnoll, \& Munafo, 2007; Schnoll, Johnson, \& Lerman, 2007). Polymorphisms of CYP2A6, a cytochrome P450 enzyme, play a major role in the inactivation of nicotine to its metabolite, cotinine (Messina, Tyndale, \& Sellers, 1997; Benowitz, 2008).

Specific Aims. The primary specific aim is to compare the effects of the experimental group to the attention control group on smoking-related mental representations, appraisals, behaviors, and affective responses over time. The primary aim will be achieved using a randomized, longitudinal, two-group repeated measures design to determine the direct effects of the intervention on smoking-related mental representations, appraisals, behaviors, and affective responses.

The secondary aim is to explore whether personality characteristics (trait negative affectivity and curiosity) and educational level moderate the effects of the genetic educational program on smoking-related mental representations, appraisals, behaviors, and affective responses.

The secondary aim will be achieved with multiple and logistic regression to determine whether personality traits and educational level moderate the effects of the intervention on the identified smoking-related outcomes.

Methods. Participants will be assigned randomly to either the experimental or attention control groups. The groups will be balanced for gender and number of cigarettes smoked per day using stratified randomization (Friedman, Furberg, \& DeMets, 1996). Age and baseline data for major study variables will be treated as covariates.

The experimental group, referred to as the Genetic Education Session (GES) group, will receive education about two smoking-related genotypes, DRD2 and CYP2A6. The content of GES session one is basic genetics and includes concepts and terminology, the impact of the Human Genome Project on health-care and the use of genetic counseling and testing. The content of GES session two is research about smoking and genetics. The content focuses on the multifactorial nature of smoking; research findings about genetic contributions to smoking, specifically for candidate genotypes DRD2 and CYP2A6; and potential applications of this research for cessation treatment, including legal, ethical and social implications of genotyping. To control for an attention placebo effect (Meltzoff, 1998), the control group will receive information about nutritional guidelines as established by the U.S. Department of Agriculture (USDA) and FDA. The attention control group will be referred to as the Nutritional Education Session (NES) group. The content of NES sessions one and two are aimed at understanding and using dietary and food safety guidelines. Following the genetic or nutritional education sessions, both groups will receive a standard cognitive-behavioral smoking cessation intervention with NRT in the form of transdermal nicotine (TN) patch. This intervention will be referred to as the standard smoking cessation (SSC) sessions. SSC content focuses on the: (a) nature of nicotine addiction; (b) use of self-change strategies in the form of self-monitoring, stimulus identification and control, stress management, and relapse prevention; and (3) use of nicotine replacement to manage craving and withdrawal symptoms. The SSC sessions consists of four 2-hour group counseling sessions and one follow-up telephone call after the last session. The intervention will occur over a 5-week period after the GES or NES. Participants will receive a 6-week supply of TN patches in the following dosages: 21 mg/24hours for 4 weeks and 14 mg/24 hours for 2 weeks (Fiore Jaen, Baker al., 2008). A 1-week supply of patches will be distributed during SSC sessions 2-3 and a 2-week supply will be distributed at session 4. The final two weeks of free TN in 14 mg/24hours strength will be mailed to participants' homes during week 7. Participants will be encouraged to purchase a two-week supply of the 7 mg/24hours patches for the final two weeks of an 8-week course of TN. They will also have the option of using combination therapy as recommended in the 2008 guideline, to augment the TN with other NRT (gum, spray, inhaler) or bupropion SR. This option will be explained at the time of obtaining informed consent so participants can visit their primary care provider to obtain prescription medication (nicotine spray or inhaler or bupropion SR) prior to the SSC. Data will be collected on use of TN alone or in the recommended combinations. Expired air CO measurements will be conducted at each Session as feedback/motivation for participants. Session 1 CO measurement will be used as the baseline CO data.

Data Collection. Data collection in the form of self report questionnaires will occur at four time points, Time 1 through Time 4 (T1-T4). Baseline data collection (T1) will be followed by randomization to the experimental or control group. T2 data will be collected in two parts (T2a\&b) to obtain initial post-intervention data for variables pertaining to each of these sessions: T2a will occur at the end of the education sessions (GES or NES) and T2b will occur at the end of the SSC sessions (i.e., 6 weeks). T2a Questionnaires will be distributed at the end of these sessions and return by the start of the SSC (Week 3). T2b questionnaires will be distributed at the end of the SSC. Questionnaires will be returned by postage-paid mail by Week 8. If needed, participants will be reminded to do this at the follow-up telephone session. Two additional data collections (T3-T4) will occur at twelve weeks and 6 months after the end of the SSC. T3-T4 data will consist of self-report questionnaires and in-person measurement of expired air CO with salivary cotinine verification of abstinence for participants not using NRT and whose CO measurement is \<8-10 ppm (Benowitz et al., 2002).

Data Analysis. Preliminary analyses of the dependent variables will include frequency distributions to look for outliers, descriptive statistics and plots to assess normality, and bivariate scatterplots to evaluate linearity of relationships among study variables. Statistical methods of dealing with nonnormality, such as transformations of the raw data, may be employed prior to analysis. For all scales, internal consistency reliability coefficients will be estimated. All primary analyses will be based on an intent-to-treat paradigm. Each participant's data will be analyzed according to their randomized assignment, regardless of whether they completed all intervention sessions. The analysis plan will be carried out in order to work out any methodological issues, but because this is not a fully powered study, significant findings are not expected at the .05 level. A more liberal level of .10 will be used for significance tests, and emphasis will be placed on descriptive statistics and estimating effect sizes.

For Aim 1, the primary endpoint of mean change over time relative to baseline will be compared for the experimental and control groups using Generalized Estimating Equations (GEE) methodology (Laing \& Zeger, 1986). A model will be fit incorporating terms to test the effects of the intervention and time, covarying for baseline values, for age, and for amount smoked. An interaction term will also be included to test whether the rate of change over time is the same for both groups. If difficulties occur with implementing GEE because of the relatively small number of cohorts per group in the pilot study, the model may be simplified to a cross-sectional analysis with individuals nested within cohorts at each time point.

For Aim 2, multiple and logistic regression will be used to predict the outcome variables from the independent variables and tests of moderation will be conducted according to procedures described by Baron \& Kenny (1986).

Eligibility criteria: Inclusion Criteria:

* Current Smoker
* Smoking ten or more cigarettes per day
* 19 years or older
* Intention of quitting smoking in the next month
* Agree to use two forms of acceptable birth control while using the nicotine replacement patch

Exclusion Criteria:

* Not currently seeking treatment for a mental disorder with psychotic symptoms
* Not currently pregnant nor nursing
* Not been recently diagnosed or currently affected with cancer or any other life-threatening illness
* No recent heart attack
* No history of high blood pressure or not currently receiving treatment to manage high blood pressure
* No history of an irregular heartbeat
* Not currently taking medications to help quit smoking (i.e. Chantix, Zyban or Wellbutrin, NRT)
* No history of adverse effects from using nicotine replacement patches
* Not currently experiencing serious pain or discomfort due to heart disease

Primary outcomes:
measure: Knowledge of Genetic Contributions to Smoking
timeFrame: One week after completion of the two Educational Sessions (GES or NES). Educational sessions occurred over two weeks.
measure: Smoking-Related Appraisals
timeFrame: Six weeks after the baseline data collection, which was the end of the Smoking Cession Sessions.
measure: Smoking Abstinence at End of Smoking Cessation Sessions
timeFrame: Six weeks, which was the end of the Smoking Cessation Sessions.
Secondary outcomes:
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Julia F Houfek, PhD, RN
role: PRINCIPAL_INVESTIGATOR
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