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

BackgroundSmoking 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. MethodsA 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 [&le;] 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. DiscussionThis 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. Trial registrationClinicalTrials.gov ID: NCT04452175. Registered June 29, 2020.