Pilot Study of Nicotine Nasal Spray and Varenicline on Smoking in Methadone-Maintained Patients

Smoking prevalence is over 83% in methadone-maintained patients. These patients experience
significant difficulty quitting, and there is evidence that a majority of
methadone-maintained patients smoke most of their cigarettes in the 4 hours following
methadone dosing. The objective is to provide a preliminary test of the ability of two
pharmacological treatments, the nicotine nasal spray and varenicline, relative to placebos,
to reduce smoking during the 4 hours following methadone dosing.

Inclusion Criteria:

1. be male or female, 18 years of age or older

2. be able to understand the study, and having understood, provide written informed
consent in English

3. have been enrolled in the University of Cincinnati Physicians Company-Opioid Treatment
Program (UCPC-OTP) program for at least 30 days and be stable on the current methadone
dose for at least 1 week

4. have smoked cigarettes for at least 3 months, have a measured exhaled carbon monoxide
(CO) level > 8 parts per million (ppm), and not planning to seek smoking-cessation
treatment within the next 3 months

5. have a willingness to comply with all study procedures, including trying to stop
smoking during designated weeks, and to comply with medication instructions

6. based on a week of Quitbit cigarette lighter assessments, with at least 5 days of
usable data, smoke ≥ 10 cigarettes/day and smoke at least 30% of daily cigarettes
within the 4-hour post-methadone-dosing period

7. if female and of child bearing potential, agree to use one of the following methods of
birth control: oral contraceptives, contraceptive patch, barrier (diaphragm or
condom), intrauterine contraceptive system, levonorgestrel implant,
medroxyprogesterone acetate contraceptive injection,complete abstinence from sexual
intercourse, hormonal vaginal contraceptive ring.

Exclusion Criteria:

1. have a current or past diagnosis of any psychotic disorder, or bipolar I or II
disorder

2. have a psychiatric condition that, in the judgment of the study physician would make
study participation unsafe or which would make treatment compliance difficult

3. be a significant suicidal/homicidal risk

4. have a medical condition that, in the judgment of the study physician, would make
study participation unsafe or which would make treatment compliance difficult. Such
conditions include, but are not limited to:

- liver function tests greater than 3 times upper limit of normal

- serum creatinine greater than 2 mg/dL

5. have had clinically significant cardiovascular or cerebrovascular disease within the
past 6 months or have clinically significant ECG abnormalities

6. have taken an investigational drug within 30 days before consent

7. be taking concomitant medications that are contraindicated for use with the NNS or
varenicline

8. be taking any concomitant medications that could increase the likelihood of smoking
cessation (such as wellbutrin or nortriptyline)

9. have a known or suspected hypersensitivity to varenicline or the nicotine nasal spray
(NNS)

10. use/have used smoking-cessation counseling programs with individual counseling or
smoking-cessation medication treatments currently, or within 30 days before consent

11. have used electronic cigarettes or tobacco products, other than cigarettes, in the
week before consent

12. be pregnant or breastfeeding

13. be anyone who, in the judgment of the investigator, would not be expected to complete
the study protocol (e.g., due to relocation from the clinic area, probable
incarceration, etc.)