A 12-month randomised, double-blind, controlled, multicentre trial comparing changes in Cigarette consumption after switchinG to high or low nicotine strENght E-cigaretteS In smokers with Schizophrenia spectrum disorders: Protocol for the GENESIS Trial

Background: Smoking prevalence among people with mental disorders is about two to four times higher than in the general population. As a result of high smoking rates, people with a mental health condition also have high rates of morbidity and mortality from smoking-related diseases compared with the general population. Progress in reducing smoking prevalence in people with mental health diagnoses has been very slow compared to the general population. Consequently, there is a pressing need for alternative and more efficient interventions to reduce or prevent morbidity and mortality in smokers with schizophrenia spectrum disorders. Methods: A volunteer population of 258 adult smokers with Schizophrenia Spectrum Disorder will be recruited for the GENESIS study, a randomized, double blind, smoking cessation trial comparing effectiveness, safety and subjective effects between 5% and 1.5% nicotine e-cigarette. The study duration will be 12-month. The primary endpoint of this study will be the continuous quit rate defined as the proportion of study participants who self-report that they had stopped smoking at 6-month, biochemically verified by exhaled CO measurements of < 7 ppm. These participants will be referred to as Quitters. The differences in continuous variables between the two groups for normally distributed data will be evaluated by one-way analysis of variance (ANOVA). The differences between the two groups for not normally distributed data will be evaluated by the Mann-Whitney U test. Any correlation between the variables under evaluation will be assessed by Spearman r correlation. To analyze differences in frequency distribution of categorical variables we will use the Chi-square test with the Yates correction or the Fisher exact test. All statistical tests are two-tailed and are considered to be statistically significant at a P value <0.05. The consistency of effects for pre-specified subgroups will be assessed using tests for heterogeneity. Subgroups will be based on age, sex, education, level of nicotine dependence. Discussion: This will be the first multicenter randomized trial directly comparing high (JUUL 5% nicotine) with low nicotine strength devices (JUUL 1.5% nicotine) in term of reduction in cigarette consumption, adoption rates, product acceptability, tolerability, and tobacco harm reduction potential. This knowledge can contribute to a better understanding of e-cigarette with high nicotine content as a pragmatic and much less harmful alternative to tobacco smoking with the possibility of significant health gains in smokers with schizophrenia spectrum disorders.