Nicotine Receptor Density & Response to Nicotine Patch: Pt 2 Extended Treatment

Study Overview
=================
Brief Summary
-----------------
The study investigators will enroll 45 treatment seeking, cigarette smokers with a Diagnostic and Statistical Manual (DSM-IV) diagnosis of schizophrenia who will be randomly assigned into three arms of treatment for smoking cessation treatment, receiving either 1. Control: standard therapy (n=15), including stepwise monotherapy of nicotine patch or bupropion sustained release, 2. Extended treatment with combination bupropion, nicotine patch, and nicotine lozenge for 6 months (n=15), or 3. Extended treatment with combination bupropion, nicotine patch, and nicotine lozenge for 6 months with home visits (n=15) and phone calls to the home or living facility. During all treatments, participants will receive weekly smoking cessation group counseling, as is standard for smoking cessation treatment. At the time of enrollment, participants will complete a one-study visit lead-in to complete baseline assessments, psychological and medical evaluation, and comprehensive assessment of drug use to determine study eligibility. Once determined to be eligible for the trial, participants will be randomly assigned to one of the treatment arms using a randomization procedure. The standard therapy treatment arm, or control group, will receive either nicotine patch taper starting at 21 milligrams (mg) daily, nicotine lozenge as needed, and/or bupropion sustained release at 150mg daily for 3 days, then 150 mg twice a day for a total of 12 weeks. The extended therapy arm will start the nicotine patch at 21mg daily with as needed nicotine lozenge for breakthrough cravings and initiation of bupropion sustained release at 150mg daily for 3 days a week prior to starting nicotine replacement, then 150 mg twice daily for 6 months (as tolerated). The third arm will be identical to the second arm except for the added home visit intervention.

Official Title
-----------------
Nicotine Receptor Density & Response to Nicotine Patch: Pt 2 Extended Treatment

Conditions
-----------------
Smoking Cessation, Schizophrenia

Intervention / Treatment
-----------------
* Drug: Combination Bupropion + NRTs
* Other: Extended Treatment
* Other: Home Visits & Calls
* Drug: Monotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Veterans 21 years of age or older; meet DSM-IV criteria for Schizophrenia or Schizoaffective disorder based on clinical interview meet DSM-IV criteria for nicotine dependence must report smoking >10 cigarettes daily and positive CO exhalation >8ppm seeking treatment for nicotine dependence; willing and able to comply with study procedures; willing and able to provide written informed consent; if female, not pregnant or lactating and willing to use a medically reliable method of birth control during the trial (e.g., birth control pills, Depo-Provera, and/or condoms with spermicide). Must be clinically stable (i.e., no inpatient hospitalizations for 3 months prior to enrollment, no changes in medication in the four weeks prior to enrollment) Exclusion Criteria: current or past history of cardiovascular disease including myocardial infarction, acute coronary syndrome, angina pectoris, coronary artery disease, atrial fibrillation/flutter, cor pulmonale, arrhythmia other than sinus tachycardia or sinus bradycardia, or an EKG suggesting any of these; systolic blood pressure greater than 160 or diastolic blood pressure greater than 100 (i.e. cutoffs for stage 2 hypertension) a history of angioedema; renal impairment (CrCl < 50); a current neurological disorder (e.g., organic brain disease, dementia) or a medical history which would make study agent compliance difficult or which would compromise informed consent; a history of attempted suicide (lifetime) and/or suicidal ideation in the past year as assessed by the C-SSRS; currently on prescription medication that is contraindicated for use with bupropion; currently using any form of nicotine replacement therapy; current dependence on cocaine, opiates, alcohol, or benzodiazepines as defined by DSM-IV within the past 6 months; a history of sensitivity to bupropion or nicotine replacement; any history of seizures or seizure disorder; a history of serious head injury (ie, loss of consciousness longer than 1 hour, no neuropsychological sequelae, no cognitive rehabilitation treatment post head injury evidence of substance or alcohol dependence in the past six months; evidence of substance or alcohol abuse in the past month; sedatives or benzodiazepine use within 12 hours of testing based on urine toxicology screening history of mental retardation or developmental disability based on chart review psychiatric hospitalization during study participation history of an eating disorder have a medical condition that could be made worse by treatment with nicotine, including poorly controlled insulin dependent diabetes, uncontrolled hyperthyroidism, pheochromocytoma, severe oropharyngeal, esophageal, or peptic ulcer disease, or severe renal or hepatic impairment as determined via the baseline medical history and physical exam have an allergy to adhesive tape or latex or serious dermatologic disease (excluding minor skin conditions such as mild eczema) due to potential for skin allergy to patch have a known allergy to nicotine or any component of the nicotine patches be pregnant or sexually active and not using reliable birth control methods consistently (for females)

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard Monotherapy<br>Treatment as usual starting with one smoking cessation medication plus group therapy. | Drug: Monotherapy<br> <br> |
| Experimental: Combination Extended Treatment<br>Extended treatment with multiple standard medications plus group therapy. | Drug: Combination Bupropion + NRTs<br> <br> Other: Extended Treatment<br> <br> |
| Experimental: Combination Extended Treatment + Home Visits/Calls<br>Extended treatment with multiple standard medications plus group therapy plus home visits. | Drug: Combination Bupropion + NRTs<br> <br> Other: Extended Treatment<br> <br> Other: Home Visits & Calls<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exhaled Carbon Monoxide (CO) as Parts Per Million (PPM) | Weekly measurements of expired carbon monoxide in the units of parts per million (PPM) participants to evaluate abstinence from smoking (a value equal to or less than 3 PPM is considered abstinent). | Measured week 0, 12, and 26 |