R01-Williajm - Double-Blind Placebo-Controlled trial of Nicotine Nasal Spray as a

DESCRIPTION (provided by applicant): Smokers with schizophrenia have been under-studied yet smoke at increased rates and suffer disproportionate tobacco-caused disease. To date there have been no placebo controlled trials of Nicotine Replacement Therapy (NRT) in schizophrenia and open label nicotine patch studies have yielded quit rates of about half that seen in other smokers. Our studies showing higher serum nicotine levels in schizophrenia (Williams et al., 2005) indicate a need for nicotine delivery treatment that more closely resembles smoking. Nicotine Nasal Spray (NNS) differs from other forms of NRT in that nicotine is absorbed rapidly through the nasal mucosa and produces physiological effects that are expected to speed relief of withdrawal and craving. Our clinical experience and human laboratory experiments indicate good tolerability and utilization of NNS as well as reduced craving in subjects with schizophrenia. This R01 grant application describes a randomized, double-blind, placebo-controlled trial of nicotine nasal spray as an aid for smoking cessation in 120 individuals with schizophrenia. The primary aims of this study are to: 1) Determine if nicotine nasal spray is more effective than placebo nasal spray as an aid for smoking cessation in individuals with schizophrenia, 2) Determine if nicotine nasal spray reduces the severity of symptoms of nicotine withdrawal and urges to smoke as compared to placebo nasal spray in smokers with schizophrenia. Subjects will be instructed to use the nasal spray at a minimum of 8 doses each day and up to a maximum of 5 doses per hour and 40 doses in 24 hours starting on the Target Quit Date (TQD) and through the end of Week 20. Quit rate will be defined as the proportion of individuals who self report tobacco abstinence during weeks 5 through 8 confirmed by exhaled carbon monoxide (CO) less than 10 parts per million (ppm). Both groups will receive behavioral intervention designed for schizophrenia delivered as 15 sessions over 26 weeks. Secondary objectives are to: 1) Determine if nicotine nasal spray is more effective than placebo nasal spray as an aid for smoking cessation in individuals with schizophrenia at Study Weeks 12, 20, 26 and 52, 2) Determining if initial positive effects from first time use of the NNS as measured by the Initial Spray Experience (ISE) scale predict subsequent use of NNS and cessation in smokers with schizophrenia, and 3)Determine the safety of NNS versus placebo NS for smoking cessation in smokers with schizophrenia as assessed by adverse events and vital signs. PUBLIC HEALTH RELEVANCE: People with schizophrenia are nearly three times as likely to smoke as the general population, with heavy smoking occurring commonly. Smoking caused diseases are also common in individuals with schizophrenia, with recent estimates of 25 years of life lost, much of which is attributable to smoking. Smokers with schizophrenia are approximately half as likely to quit smoking as smokers without a major mental illness for reasons that are still poorly understood. There is a need to systematically examine available treatments and explore new ones that can address their needs.