Electronic Nicotine Delivery Systems as a Smoking Cessation Treatment

Cigarette smokers, who are motivated to quit smoking but who rate the inhalation aspects of
smoking as important will be randomized to three groups: Group 1. Nicotine ENDS + nicotine
patch; Group 2: Nicotine ENDS + placebo patch; Group 3: Placebo ENDS + Nicotine patch.
Participants will initially receive 1 week of 21 mg nicotine (or placebo) skin patches while
continuing to smoke their usual cigarettes ad lib, in order to assess responsiveness to
Nicotine Replacement Therapy (NRT). Starting with week 2, participants will receive
nicotine-containing (or placebo) ENDS devices (menthol or non-menthol versions in accordance
with their baseline preference). They will also be instructed to substitute ENDS for as many
cigarettes as possible in this week. The target quit-smoking date will occur at the beginning
of week 3. Treatments will continue until week 8 post-quit, at which time participants will
be instructed to reduce ENDS use over the next 4 weeks, at which time ENDS will no longer be
dispensed. Subsequently, the nicotine patch dose will be gradually reduced according to
standard weaning regimen from 21 mg/24 h to 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2
weeks. All nicotine-based treatments will end at week 16 after the quit date.

Inclusion Criteria:

- Have no known serious medical conditions;

- Smoke an average of at least 10 cigarettes per day;

- Have an expired air CO reading of at least 15 ppm;

- Able to read and understand English;

- Express a desire to quit smoking in the next thirty days;

- Higher than median rating of enjoyment of airway sensory effects of inhaling smoke on
Cigarette Evaluation Questionnaire.

Exclusion Criteria:

- Hypertension;

- Hypotension;

- Coronary heart disease;

- Lifetime history of heart attack;

- Cardiac rhythm disorder (irregular heart rhythm);

- Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);

- Cardiac (heart) disorder (including but not limited to valvular heart disease, heart
murmur, heart failure);

- History of skin allergy;

- Active skin disorder (e.g., psoriasis) within the last five years;

- Liver or kidney disorder (except kidney stones, gallstones);

- Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;

- Ulcers;

- Lung disorder/disease (including but not limited to Chronic obstructive pulmonary
disease (COPD), emphysema, and asthma);

- Brain abnormality (including but not limited to stroke, brain tumor, and seizure
disorder);

- History of migraine headaches in the past 5 years;

- History of fainting;

- Problems giving blood samples;

- Difficulty passing urine;

- Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less
than 180mg/dcl and HbA1c is less than 7%);

- Current cancer or treatment for cancer in the past six months (except basal or
squamous cell skin cancer);

- Other major medical condition;

- Current psychiatric disease (with the exception of anxiety disorders, Obsessive
Compulsive Disorder (OCD) and ADHD);

- Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted
suicide;

- Current depression;

- Bulimia or anorexia;

- Pregnant or nursing mothers;

- Use (within the past 30 days) of:

- Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol
(THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP),
Benzodiazepines, or Barbiturates),

- Experimental (investigational) drugs;

- Psychiatric medications including antidepressants, anti-psychotics or any other
medications that are known to affect smoking cessation (e.g. clonidine);

- Smokeless tobacco (chewing tobacco, snuff), cigars, pipes, nicotine replacement
therapy, e-cigarettes or other smoking cessation treatment;;

- Alcohol abuse;

- Significant adverse reaction to nicotine patches in the past;

- Current participation or recent participation (in the past 30 days) in another smoking
study at our Center or another research facility;

- Current participation in another research study.

Potential subjects must agree to use acceptable contraception.

Potential subjects must agree to avoid the following:

- participation in any other nicotine-related modification strategy outside of this
protocol;

- use of tobacco products other than cigarettes, including pipe tobacco, cigars,
e-cigarettes, snuff, and chewing tobacco;

- use of experimental (investigational) drugs or devices;

- use of illegal drugs;

- use of opiate medications.