A Series of Personalized Melatonin Supplement Interventions for Poor Sleep: Feasibility Randomized Crossover Trial for Personalized N-of-1 Treatment (Preprint)

BACKGROUND Poor sleep (defined by short sleep duration or poor quality) is a common condition with potential serious health consequences. Exogeneous melatonin supplements have been found to effectively improve poor sleep but have also been shown to have heterogeneity of treatment effects (HTEs) between individuals. Personalized N-of-1 trials, in which each participant is the unit of analysis, are ideal for identifying whether a treatment with high HTE is beneficial for each individual patient. OBJECTIVE This study aimed to identify the feasibility, acceptability, and effectiveness of a series of personalized N-of-1 trials of melatonin for poor sleep. METHODS This study consisted of 60 digital, personalized N-of-1 crossover trials comparing the effects of 3.0mg and 0.5mg of melatonin versus placebo for poor sleep with randomization to 1 of 2 orders. The trial was comprised of a 2-week baseline period and a 12-week intervention period. The primary outcomes were usability of the personalized trial system (measured using the System Usability Scale [SUS]) and participant satisfaction with the trial. Effectiveness outcomes included sleep duration (measured using a Fitbit activity tracker) and sleep quality (measured using the consensus sleep diary [CSD]). RESULTS Participants rated the usability of the personalized trial as acceptable (average SUS score=76.3 [standard deviation (SD)=17.1]), and 96% (55/57) of those who completed satisfaction surveys stated that they would recommend the trial to others. Importantly, indices of HTE were low for 3.0mg and 0.5mg doses of melatonin, indicating that the effect of these treatments on sleep duration and sleep quality did not substantially vary between participants and that averaged treatment responses are appropriate. Averaged participant sleep duration did not significantly differ between the 3.0mg (P=0.7) and 0.5mg (P=0.9) melatonin intervention periods and the baseline period. Additionally, regression models did not show differences between different levels of melatonin and placebo periods for sleep duration or quality. CONCLUSIONS Participant ratings of the usability of and satisfaction with this series of personalized N-of-1 trials of melatonin for sleep suggest these trials are both feasible and acceptable. However, our results show that melatonin supplements did not significantly improve sleep duration or sleep quality. Further, the treatment effects’ lack of heterogeneity between participants suggests that future use of N-of-1 trials of melatonin for poor sleep is not needed.