Varenicline and Alcohol in Inpatient Addictions Program (IAP)

The goal of this proposal is to explore the potential efficacy of varenicline for reducing
alcohol consumption among alcohol-dependent cigarette smokers. The hypothesis for the current
study is that 24 weeks of varenicline will increase alcohol abstinence rates among smokers
and decrease alcohol consumption among patients receiving inpatient addiction treatment for
alcoholism. The investigators will also explore whether varenicline has a beneficial effect
on tobacco abstinence rates in this population of tobacco users.

The investigators will conduct an open-label pilot study to determine clinical efficacy and
employ neuroimaging techniques to evaluate how glutamate and other brain metabolites
correlate to measures of alcohol craving severity and/or subsequent varenicline treatment
response. The investigators will enroll 20 subjects receiving treatment in the Mayo Clinic
Inpatient Addictions Program (IAP) and compare outcomes with patients participating in a
similar 6-month open-label study of acamprosate.

The Primary aims of this study are:

1. To obtain preliminary evidence of efficacy of varenicline (0.5 mg once daily for 3 days,
0.5 mg twice daily for days 4-7, 1 mg twice a day for remaining 23 weeks) for increasing
continuous alcohol abstinence rates at 3 and 6 months among patients with alcohol and
tobacco dependence who have completed treatment at the Mayo Clinic IAP.

2. To obtain preliminary evidence of efficacy of varenicline (0.5 mg once daily for 3 days,
0.5 mg twice daily for days 4-7, 1 mg twice a day for remaining 23 weeks) for decreasing
the number of heavy drinking days (> 5 drinks/day for men and > 4 drink/day for women)
at 3 and 6 months among patients with alcohol and tobacco dependence who have completed
treatment at the Mayo Clinic IAP.

3. To obtain preliminary data on baseline and baseline to endpoint change in CSF volume
corrected concentrations of the dorsal striatal glutamate, glutamate + glutamine, and
NAA measures through MR spectroscopy before and after 30 days of varenicline treatment
among patients with alcohol and tobacco dependence who have completed treatment at the
Mayo Clinic IAP.

Secondary aims:

1. To obtain preliminary evidence of efficacy of varenicline (0.5 mg once daily for 3 days,
0.5 mg twice daily for days 4-7, 1 mg twice a day for remaining 23 weeks) for increasing
the 7-day point prevalence smoking abstinence rates and prolonged smoking abstinence at
3 and 6 months among patients with alcohol and tobacco dependence who have completed
treatment at the Mayo Clinic IAP.

2. To assess the tolerability of varenicline (0.5 mg once daily for 3 days, 0.5 mg twice
daily for days 4-7, 1 mg twice a day for remaining 23 weeks).

Subjects will be eligible for enrollment if they:

1. Are > 18 and < 70 years of age

2. Are admitted to the inpatient addiction program (IAP) in the Generose Building at
Saint Marys Hospital

3. Have been diagnosed with alcohol dependence based on DSM-IV-TR criteria and confirmed
by Psychiatric Research Interview for Substance and Mental Disorders (PRISM)

4. Smoke at least 10 cigarettes/day for ≥ 6 months

5. Are able to participate fully in all aspects of the study

6. Have been provided with, understand, and have signed the informed consent; and

7. Agree to identify collateral individuals for contact purposes to facilitate follow-up
appointments.

Patients will be excluded from participation if they:

1. Meet DSM-IV criteria of schizophrenia or other non-affective psychotic disorder

2. Have had psychotic symptoms within the past month

3. Have an Axis I disorder requiring new pharmacotherapy

4. Have a predominant Axis II disorder

5. Have used an investigational drug within 30 days of enrollment

6. Have started Naltrexone or Acamprosate during this same IAP admission

7. Have a history (past 3 months) of drug abuse (excluding caffeine and marijuana)

8. Have active suicidality as measured by screening questions from the Columbia-Suicide
Severity Rating Scale (C-SSRS), (Posner 2008) outlined below:

a. "Yes" response to questions 1, 2, or 3 with significant intensity level endorsed
as: i. Frequency: score of 4 or 5 ii. Duration: score of 3, 4 or 5 iii.
Controllability: score of 0, 4, or 5 iv. Deterrents: score of 0, 4 or 5 v. Reasons for
Ideation: score of 1, 2, 3, 4 or 5 b. "Yes" response to question 4 c. "Yes" response
to question 5

9. Have a history of medically serious suicide attempt within 5 years

10. Have a history of any major cardiovascular events including arrhythmias, congestive
heart failure, unstable angina, acute MI or coronary angioplasty

11. Are pregnant, lactating, or of child bearing potential, likely to become pregnant
during the medication phase and not willing to use a reliable form of contraception.
Reliable forms of contraception include diaphragm or condom (with spermicidal),
injections, intrauterine device [IUD], surgical sterilization and abstinence;

12. Have clinically significant acute or chronic progressive or unstable neurologic,
hepatic, renal, cardiovascular, respiratory or metabolic disease

13. Have another household member or relative participating in the study

14. Have a known allergy to varenicline

15. Are individuals, in the investigators opinion, unable to comply with study procedures

16. Are unable to provide written informed consent in English

17. Are on hemodialysis or have a history of kidney disease.

Patients will be excluded from participation in the MR spectroscopy portion of the study if
they have:

1. Claustrophobia

2. A history of major head trauma with loss of consciousness > 5 minutes or skull
fracture

3. A history of previous neurological event (e.g., epilepsy, stroke, transient ischemic
attack)

4. Implanted metal objects (e.g., pacemakers; aneurysm clips; metal prostheses, joints,
rods, or plates)

5. Contraindication to MRI scanning.