Behavioral Activation for Smoking Cessation and the Prevention of Post-Cessation Weight Gain

This is a randomized clinical trial of the efficacy of a behavioral activation intervention
to smoking cessation and to post-cessation weight gain (BAS+) plus transdermal nicotine (TN)
compared to standard smoking cessation counseling (SC) plus TN in treatment-seeking smokers.
After completing an Intake Visit (~week -3), eligible smokers will be randomized (stratified
by nicotine dependence, BMI and gender) to participate in 8 individual sessions of BAS+ or SC
over a 10-week treatment period with two sessions prior to the target quit date (weeks -2,
-1) and six sessions post-target quit date (TQD [week 0] and weeks 1, 2, 4, 6, and 8).
Standard, 8-week; open-label TN will begin on the TQD. Moderators will be assessed
pre-treatment. Mediating mechanisms will be assessed before, during, and at the end of
treatment (EOT, week 8). Smoking will be assessed by self-report and biochemically confirmed
(Carbon Monoxide [CO] < 5) at all in-center visits after quitting, at EOT (week 8), and at
the 12- and 26-week follow-ups. Weight will be assessed at these same time points. Food
intake will be measured by three consecutive days of 24-hour food recalls at Baseline [week
-2] and 4-, 8-, and 12- and 26-weeks post-TQD. Smoking cessation and post-cessation weight
gain (PCWG) are the primary outcomes and food intake is a secondary outcome at 26-weeks
post-TQD. Consistent with intent-to-treat (ITT) analyses, the investigators will measure
smoking cessation and weight gain in the full sample at the 26-week follow-up, evaluating a
smoking status by treatment interaction for the PCWG analysis.

Inclusion Criteria:

- Male and female treatment-seeking smokers who are between 18 and 65 years of age and
self-report smoking at least 5 cigarettes (menthol and/or non-menthol) per day for at
least the last 6 months.

- Plan to live in the area for the duration of the study (i.e. ~30 weeks/8 months).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the combined consent and HIPAA form.

- Smokers who wish to make a permanent quit attempt in the next 1-2 months
(treatment-seeking), because our prior work suggests that motivated subjects are more
sensitive to medication effects on smoking behavior.

- Able to communicate fluently in English (i.e. speaking, writing, and reading).

- Provide a Carbon Monoxide (CO) breath test reading greater than or equal to 8 parts
per million (ppm) at the Intake Visit.

Exclusion Criteria:

Smoking Behavior.

- Regular use of nicotine containing products other than cigarettes (e.g. chewing
tobacco, snuff, snus, cigars, e-cigs, etc.). Participants agreeing to abstain from
using nicotine containing products other than cigarettes and the study-provided TN for
the duration of trial will be considered eligible.

- Current enrollment or plans to enroll in another research and/or smoking cessation
program over the duration of the study (i.e. ~30 weeks/8 months).

- Anticipated use (within the next ~30 weeks/8 months) of any nicotine substitutes
and/or smoking cessation treatments/medications unless provided through the study.

- Provide a CO breath test reading less than 8 ppm at Intake Visit.

Alcohol and Drug.

- History of substance abuse (other than nicotine) in the past 12 months and/or
currently receiving medical treatment for substance abuse. Counseling and support
groups (e.g. Alcoholics Anonymous and Narcotics Anonymous) will not be considered
medical treatment for the purposes of this protocol.

- Current alcohol consumption that exceeds 25 standard drinks/week.

- Breath alcohol reading (BrAC) greater than .000 at the Intake Visit.

- A positive urine drug screen (UDS) for cocaine, opiates, amphetamines,
methamphetamines, phencyclidine (PCP), ecstasy (MDMA), barbiturates, benzodiazepines,
methadone, and/or oxycodone at the Intake Visit.

Medical.

- Women who are pregnant, breast feeding, or planning a pregnancy over the duration of
the study period. Women must agree to use an adequate form of contraception or abstain
from sexual intercourse for the duration and for at least one month after the end of
the study.

- Current treatment of cancer or diagnosed with cancer (except basal or squamous-cell
carcinoma not treated with chemotherapy and/or radiation) in the past 6 months.

- Poorly controlled, brittle, or pump-dependent Type I diabetes.

- Current peptic ulcer bleeding.

- Allergy to adhesive tape.

- Skin problems or sensitivities. Eligibility will be evaluated on a case-by-case basis
by the Study Physician.

- Active hepatitis or poorly controlled kidney and/or liver disease.

- Uncontrolled hypertension (systolic blood pressure [SBP] greater than 159 and/or
diastolic blood pressure [DBP] greater than 99

- History of abnormal heart rhythms, tachycardia, and/or cardiovascular disease (e.g.
stroke, angina, heart attack) may result in ineligibility. These conditions will be
evaluated on a case-by-case basis by the Study Physician.

- History of epilepsy or seizures. Eligibility will be evaluated on a case-by-case basis
by the Study Physician.

- Serious or unstable disease within the past 6 months. Notable diseases will be
evaluated on a case-by-case basis by the Principal Investigator and/or the Study
Physician.

- Any impairment including, but not limited to, visual, physical, and/or neurological
impairments preventing proper completion of the study procedures. Notable impairments
will be evaluated on a case-by-case basis by the Principal Investigator and/or the
Study Physician.

- Low or borderline intellectual functioning - determined by receiving a score of less
than 85 on the Shipley Institute of Living Scale (SILS), which correlates with the
Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated Intelligence Quotient
(IQ) Test.

- Applicable food allergies or disorders:

Galactosemia, Notable milk allergy (lactose intolerant participants may proceed unless they
experience severe symptoms), Notable soy allergy, Peanut allergy

Psychiatric.

- Current diagnosis of major depression. Subjects with a history of major depression, in
remission for 6 months or longer (may be stable on antidepressant medications), are
eligible.

- Lifetime history of a suicide attempt.

- Lifetime history of schizophrenia, psychosis, and/or bipolar disorder.

Medication.

Current use or recent discontinuation (within the last 14 days) of:

- Smoking cessation medication (e.g., Zyban, Wellbutrin, Wellbutrin Standard-Release,
Chantix).

- Benzodiazepines and/or Barbiturates.

- Anti-psychotic medications.

- Prescription stimulants (e.g., Provigil, Ritalin, Adderall).

- Systemic steroids.

Current use of:

- Nicotine replacement therapy (NRT).

- Heart medications such as digoxin, quinidine, and nitroglycerin.

Daily use of:

- Opiate-containing medications for chronic pain.

- Inhaled corticosteroids.

General Exclusion.

- Past, current, anticipated, or pending enrollment in another research program over the
study period that could potentially impact subject safety, study data, and/or the
study design as determined by the Principal Investigator and/or Study Physician.

- Any medical condition, illness, disorder, adverse event (AE), or concomitant
medication that could compromise participant safety or significantly impact study
performance as determined by the Principal Investigator and/or Study Physician.
Subjects may be deemed ineligible for any of the aforementioned reasons at any point
throughout the study, as well as during the initial telephone screen.

- Significant non-compliance with protocol and/or study design as determined by the
Principal Investigator and/or Study Physician. Subjects may be deemed ineligible at
any point throughout the study.

- Subjects failing to complete an in-person Baseline Visit will be excluded (no
Principal Investigator determination required).