Tobacco Cessation: Treatment Delivery and Predictors of Outcome

Objective

The purpose of this protocol is to create a mechanism whereby the intramural program of the
NIDA in Baltimore, MD can evaluate and treat a broad range of people who use tobacco
products. Through this protocol, participants will receive state-of-the-art treatment for
their tobacco use. The secondary objective is to investigate predictors of success in
tobacco-use-cessation treatment.

Study population

Participants will be individuals who present to the NIDA IRP seeking to quit tobacco use
(smoked and smokeless). Enrollment may occur as part of participation in another NIDA IRP
study. We will enroll up to 1000 participants. All individuals who give signed informed
consent and who attend at least one study visit will be considered evaluable. We will not
replace study dropouts.

Design

After undergoing initial screening and signing the IRB-approved consent form, participants
will be enrolled in our outpatient smoking treatment-research clinic at the NIDA IRP. The
study will last up to one year, with active treatment lasting up to 36 weeks and follow-up
visits 4, 6, and 12 months after the first treatment visit. Treatment will include
counseling and pharmacotherapy (nicotine replacement, bupropion, or varenicline, if
warranted and medically appropriate). During active treatment, participants will visit the
clinic up to twice a week for counseling, dispensing of medication, and monitoring of
tobacco use, withdrawal symptoms, and reporting of any adverse events. Visits may take up to
90 minutes.

Outcome measures

There are no outcome measures for the primary objective. For the secondary objectives, the
outcome measures are (1) tobacco abstinence, as determined by self-reported tobacco use,
urinary cotinine, and (in tobacco smokers only) breath CO, and (2) reduction in tobacco use
of at least 50% (e.g., from 10 cigarettes per day to 5 cigarettes per day). Other outcome
measures for the secondary objectives include duration of abstinence, nicotine withdrawal
signs and symptoms, and tobacco craving. Behavioral, psychological, medical, and genetic
characteristics and tobacco-use history will be assessed at the beginning of the study as
predictors of treatment outcome and at follow-up.

- Participants will be individuals who present to the NIDA IRP seeking help to quit
tobacco use (smoked or smokeless). We will enroll up to 1000 participants. All
individuals who give signed consent and attend at least one study visit will be
considered evaluable. We will not replace study dropouts.

INCLUSION CRITERIA:

1. 18 years of age or older

2. Seeking help for cessation of tobacco use

EXCLUSION CRITERIA:

1. Inability to give informed consent.

2. Current use (within the past 30 days) of any of the 7 FDA-approved first-line
smoking-cessation treatments (varenicline, bupropion, or NRTs such as a nicotine
inhaler, lozenge, patch, gum, or nasal spray), unless administered as part of another
NIDA IRP protocol.

3. Any newly diagnosed or untreated acute medical illness that requires immediate
medical attention. This includes any new medical diagnosis (for example, diabetes or
hypertension) in someone who is not under the care of a physician and/or that is not
well controlled. An untreated acute medical illness would include acute hepatitis,
acute pancreatitis, acute respiratory distress syndrome, etc. Individuals may be
considered for participation once a newly diagnosed condition is well controlled or
an acute condition has resolved.

ADDITIONAL EXCLUSION FOR NRT:

1. Current major medical conditions that in the view of the investigators would
compromise the integrity of the data or the safety of the participant, including
moderate to severe cardiovascular disease (30 days post-MI, severe or worsening
angina pectoris), life-threatening arrhythmias, acute phase cerebrovascular accident,
COPD (emphysema and chronic bronchitis).

2. Current uncontrolled psychiatric condition that in the view of the investigators
would compromise the integrity of the data or the safety of the participant,
including bipolar disorders and any psychotic disorder. Uncontrolled psychiatric
condition includes but is not limited to: psychiatric medication change in the last 3
months; or psychiatric exacerbation or related hospitalization in the last 3 months.
Individuals with controlled Major Depressive Disorder under the care of a
psychiatrist or internist may be considered for inclusion.

3. Pregnancy

4. Lab values outside of the values listed in Table 1 below.

5. Nicotine patch only: allergy to adhesive tape, generalized chronic dermatological
disorders, weight < 45kg, and/or lactation

ADDITIONAL EXCLUSION CRITERIA FOR VARENICLINE OR BUPROPION:

1. Pregnancy or nursing

2. Current diagnosis of schizophrenia or any other DSM-IV psychotic disorder, bipolar
disorder, panic disorder, eating disorder (current or prior diagnoses), Major
Depressive Disorder within the past year requiring treatment, or history of suicide
attempt

3. History of seizures, except for febrile seizures in childhood

4. Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines

5. Lab values outside of the values listed in Table 1 below

6. Unstable cardiovascular disease or cardiovascular events occurring within two months
before screening

7. For bupropion only: current administration of monoamine oxidase inhibitors (MAO-I);
at least 14 days must elapse between discontinuation of an MAO-I and initiation of
treatment with bupropion; current administration (within past 30 days) Wellbutrin,
Wellbutrin SR, Wellbutrin XL.