Carcinogen Exposure and Risk Reduction Among Smokers Randomized to a Tobacco Potentially Reduced-Exposure Product (PREP) or Medicinal Nicotine:

A Feasibility Study

Jennifer Guzi, RN, BSN, MSNc, FNPc Andrea Prados, RN, BSN, MPH, MSNc, FNPc Georgetown University School of Nursing and Health Sciences

Acknowledgments

American Cancer Societys Institutional Research Grant University of Minnesota QUEST Study Research Team- PI, Dorothy Hatsukami, PhD & Project Coordinator, Joni Jensen, MS Georgetowns QUEST Study Research Team
{ { { { { { {

Janie Heath, PhD, APRN-BC Peter Shields, MD Stephanie Spernak, PhD Colleen Lynch, MS Zumei Feng, MD Jerry Taddeo, BS, MS, MTASCP FNP Student Researchers: Jennifer Guzi, Andrea Prados, Colleen Pierce, Morgane Swift NHS Student Interns: Warren Sizemore, Enela Zyka

State-Specific Prevalence of Smoking among Adults, 2004

Kentucky 27.6%

Maryland 20.2% DC 20.8%

44.5 Million Adult Smokers Utah 10.5%

Virginia 20.8%

Centers for Disease Control and Prevention. (2005). MMWR 54:11241127.

Compounds in Tobacco Smoke

An Estimated 4,800 Compounds in Tobacco Smoke
Gases (~500 isolated)
Carbon Monoxide Hydrogen Cyanide Ammonia Benzene Formaldehyde

Particles (~3,500 isolated)

Nicotine Nitrosamines Lead Cadmium Polonium-210

Annual U.S. Deaths Attributable to Smoking, 19972001

Cardiovascular 137,979 diseases Lung cancer 123,836 Respiratory diseases 101,454 Second-hand smoke 38,112 Cancers other than 34,693 lung Other 1,828
Percentage of all smoking-attributable deaths*

32% 28%

23% 9% 8% <1%

TOTAL: 437,902 deaths annually

Centers for Disease Control and Prevention. (2005). MMWR 54:625628.

Background

Vector Tobacco Company markets a 3-step approach to becoming smoke free with Quest Cigarettes Quest 1 = Low nicotine (0.6mg) Quest 2 = Extra low nicotine (0.3mg) Quest 3 = Nicotine- free (0.05mg)

Background

No evidence currently addresses the efficacy of using Quest Cigarettes No evidence currently addresses the tobacco toxin uptake from Quest Cigarettes No evidence currently exists for cessation outcomes when comparing Quest Cigarettes and FDA approved medicinal nicotine among smokers

Quest Study Enrollment

Summer Semester 2005: n=20 Fall Semester 2005: n=20 Spring Semester 2005: n=20

Research Purpose

A pilot study to demonstrate capability to carry out a large clinical trial to study the health and behavioral effects of potential reduced exposure products (PREPS) and a smoking cessation intervention. Data (to be pooled with similar data from the University of MN) will support RO1 application and other funding mechanisms.

Hypothesis #1

Differences in cessation outcomes will be observed with individuals randomized to receive nicotinefree Quest cigarettes, extra-low Quest cigarettes and Commit lozenges.

Hypothesis #2

Differences in health effects will be observed with individuals randomized to receive nicotinefree Quest cigarettes, extra-low Quest cigarettes and Commit lozenges.

Research Design

12 week, randomized clinical trial

{

Group 1 = Quest 0.05mg nicotine & weekly counseling Group 2 = Quest 0.3mg nicotine & weekly counseling Group 3 = Commit 2mg lozenge & weekly counseling

Research Method

Sample Recruited 60 subjects over 12 months

{ { {

Males and Females Age = 18 70 Smoking between 10 40 cigs/day for past yr Smoking light, ultralight, and menthol cigarettes

Research Method

Procedure { 2 week orientation/evaluation while smoking own cigarettes { Treatment timeline = on product (Quest #2 or Quest #3 or Commit) x 6 weeks { Cessation timeline = off product x 6 weeks { 12 visits include behavioral measures, biological measures, product, & counseling

Research Measures

Biomarkers for tobacco exposure

{ { {

Biomarkers for CV disease

Lipoproteins (total cholesterol, HDL & LDL) { Triglycerides, apoprotein A-1 & B concentrations { C-reactive protein { Fibrinogen { WBC { Vital signs & weight Biomarkers for pulmonary function/lung disease { FEV1, FVC, PEF, FEV% { (PAH)-DNA adducts & chromosome aberrations { Self-reported respiratory sx { CO readings
{

Blood & urine cotinine Urinary anatabine Alveolar carbon monoxide

Biomarkers for carcinogen exposure

{ { { { { { { {

NNAL & NNAL-glucuronides 1-hydroxypryrene Muconic acid Mercapturic acids of acrolein & butadiene Phenanthren tetrol Urine mutagenicity NNN 1-HOP

Research Measures

Genotyping to assess treatment response

{ { { { { { { { {

Behavioral measures
{

CYP2A6 CYP2B6 SLC6 A3 DRD2 Dopamine transporter Dopamine D2 & D4 receptor Dopamine B hydroxylase Catechol methyltransferase Monamine oxidase

{ { { { { { { { { { { {

Topography

Medical history, respiratory sx Demographics Smoking intake & diaries Fagerstrom questionnaire Cigarette Dependence Scale Reasons for smoking WISDM Withdrawals symptoms Intention to quit-ladder Motivation & self-efficacy PANAS Q-DIS CES- Depression

Protocol

Baseline 1 = { Check in: questionnaires { Lab: VS, WT, CO, FEV1, Serum, Urine, Mouthwash, Butt Bags { Counseling: review diaries, distribute product { Check out: review completion of questionnaires, schedule next appt, payment, complete checklist

Baseline 2 = { Check in: questionnaires { Lab: VS, WT, CO, Serum, Urine, Mouthwash, Butt Bags, Typography { Counseling: review diaries, distribute product { Check out: review completion of questionnaires, schedule next appt, payment, complete checklist

Protocol

Visit 1 = tx week
{ { { {

Visit 4 = tx week
{ { { {

Check in questionnaires Lab: VS, WT, CO Counseling Check out process

Check in questionnaires Lab: VS, WT, CO Counseling Check out process Check in questionnaires Lab: VS, WT, CO, FEV1 Counseling Check out process Check in questionnaires Lab: VS, WT, CO, FEV1, Typography, Serum, Urine, Mouthwash, Quest = Butt Bags & Typography Counseling Check out process

Visit 2 = tx week
{ {

Visit 5 = tx week
{ { { {

{ {

Check in questionnaires Lab: VS, WT, CO, FEV1, Typography, Serum, Urine, Mouthwash, Butt Bags, Typography Counseling Check out process Check in questionnaires Lab: VS, WT, CO, FEV1 Counseling Check out process

Visit 6 = tx week
{ {

Visit 3 = tx week
{ { { {

{ {

Protocol

Visit 7 = off product week { Check in questionnaires { Lab: VS, WT, CO { Counseling { Check out process Visit 8 = off product { Check in questionnaires { Lab: VS, WT, CO { Counseling { Check out process Visit 9 = NO VISIT

Visit 10 = off product week { Check in questionnaires { Lab: VS, WT, CO { Counseling { Check out process Visit 11 = NO VISIT Visit 12 = off product week { FINAL Check in questionnaires { FINAL Lab: VS, WT, CO, FEV1, Serum, Urine, Mouthwash { FINAL Counseling { FINAL Check out process 4 week follow up to evaluate cessation status

Lessons Learned

The importance of methodical collection and documentation of data The outcome of the study is dependant upon the reliability and compliance of the subjects

Lessons Learned

Our background in nursing provided a strong foundation to serve as smoking cessation counselors The value of receiving tobacco cessation education PRIOR to starting study The challenges of staying on protocol or script as tobacco cessation counselors

Questions?

Part I of the FAB 4 FNP QUEST Study Journey:

{ { {

Purpose? Design? Method?

THANK YOU

FNPs Committed to Helping Patients Quit: Call 1-800 Quit Now