Evaluation of evening versus morning levothyroxine intake in elderly (MONIALE)

BACKGROUND: The aging population is associated with increased multimorbidity and polypharmacy. Older adults are at a higher risk of adverse events and reduced therapeutic response. This phenomenon is partially explained by drug interactions and treatment adherence. Most randomized clinical trials have found no significant differences between morning and evening levothyroxine (LT(4)) administration in young adults, but there is little evidence regarding alternative LT(4) regimens in older populations. Thus, the MONIALE trial aims to test an alternative schedule for LT(4) administration in older adults. METHODS/DESIGN: This randomized crossover clinical trial will include participants aged 60 years or older with primary hypothyroidism. The trial groups will consist of morning LT(4) intake (60 min before breakfast) or evening LT(4) intake (60 min after supper). The primary outcome will be variation in serum thyrotropin (TSH) levels after 24 weeks of the LT(4) protocol. The secondary outcomes will be the prevalence of drugs that potentially interact with LT(4) and hypothyroidism control according to interaction status. The sample size was calculated to detect a minimum mean difference of 1 mUI/L in serum TSH level between the groups with 80% power and a 5% probability of type I error, resulting in 91 patients per group. The project was approved by the Hospital de Clínicas de Porto Alegre Ethics Committee. DISCUSSION: Considering the aging population, the increased prevalence of multimorbidity and polypharmacy, as well as potential drug interactions and treatment adherence difficulties, an alternative LT(4) protocol could be useful for hypothyroidism treatment in the elderly. Prior studies comparing alternative LT4 administration protocols have mainly included young adult populations and have not addressed potential drug interactions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03614988. Registered 30 July 2018.