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

ABSTRACT: 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 (LT4) administration in young adults, but there is little evidence regarding alternative LT4 regimens in older populations. Thus, the MONIALE trial aims to test an alternative schedule for LT4 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 LT4 intake (60?min before breakfast) or evening LT4 intake (60?min after supper). The primary outcome will be variation in serum thyrotropin (TSH) levels after 24?weeks of the LT4 protocol. The secondary outcomes will be the prevalence of drugs that potentially interact with LT4 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 LT4 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.

SUBMITTER: Giassi K

PROVIDER: S-EPMC6918562 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Giassi Karina K Piccoli Vanessa V da Costa Rodrigues Ticiana T Gorga Bandeira de Mello Renato R

Trials 20191217 1

<h4>Background</h4>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<sub>4</sub>) administration in young adults, but there is little evidence regarding alternative LT<sub>4</sub> ...[more]

PMID: 31847914

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Project description:BackgroundVariation in blood pressure levels display circadian rhythms. The morning surge in blood pressure is known to increase the risk of myocardial events in the first several hours post awakening. A systematic review of the administration-time-related-effects of evening versus morning dosing regimen of antihypertensive drugs in the management of patients with primary hypertension has not been conducted.ObjectivesTo evaluate the administration-time-related-effects of antihypertensive drugs administered as once daily monotherapy in the evening versus morning administration regimen on all cause mortality, cardiovascular morbidity and reduction of blood pressure in patients with primary hypertension.Search strategyWe searched Cochrane CENTRAL on Ovid (4th Quarter 2009), Ovid MEDLINE (1950 to October 2009), EMBASE (1974 to October 2009), the Chinese Biomedical literature database (1978 to 2009) and the reference lists of relevant articles. No language restrictions were applied.Selection criteriaRandomized controlled trials comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in patients with primary hypertension were included. Patients with known secondary hypertension, shift workers or white coat hypertension were excluded.Data collection and analysisTwo authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Data synthesis and analysis were done using RevMan 5.1. Random effects meta-analysis and sensitivity analysis were conducted.Main results21 randomized controlled trials (RCTs) in 1,993 patients with primary hypertension met the inclusion criteria for this review - ACEIs (5 trials), CCBs (7 trials), ARBs (6 trials), diuretics (2 trials), alpha-blockers (1 trial), and beta-blockers (1 trial). Meta-analysis showed significant heterogeneity across trials.No RCT reported on all cause mortality, cardiovascular mortality, cardiovascular morbidity and serious adverse events.There was no statistically significant difference for overall adverse events (RR=0.78, 95%CI: 0.37 to 1.65) and withdrawals due to adverse events (RR=0.53, 95%CI: 0.26 to 1.07).No significant differences were noted for morning SBP (-1.62 mm Hg, 95% CI: -4.19 to 0.95) and morning DBP (-1.21 mm Hg, 95% CI: -3.28 to 0.86); but 24-hour BP (SBP: -1.71 mm Hg, 95% CI: -2.78 to -0.65; DBP: -1.38 mm Hg, 95% CI: -2.13 to -0.62) showed a statistically significant difference.Authors' conclusionsNo RCT reported on clinically relevant outcome measures - all cause mortality, cardiovascular morbidity and morbidity. There were no significant differences in overall adverse events and withdrawals due to adverse events among the evening versus morning dosing regimens. In terms of BP lowering efficacy, for 24-hour SBP and DBP, the data suggests that better blood pressure control was achieved with bedtime dosing than morning administration of antihypertensive medication, the clinical significance of which is not known.

Project description:IntroductionDrug scheduling in older adults can be a challenge, especially considering polypharmacy, physical dependency, and possible drug interactions. Properly testing alternative treatment regimens could therefore help to overcome treatment barriers. Hypothyroidism is a prevalent condition in older adults, however, studies evaluating L-thyroxine treatment effectiveness in this specific age group are still lacking. Most studies testing an evening administration of levothyroxine were mainly composed of younger adults. Therefore, this trial is aimed to assess if evening levothyroxine (LT4) administration can effectively control hypothyroidism in older patients.Materials and methodsA randomized crossover clinical trial was conducted between June 2018 and March 2020 at the Hospital de Clínicas de Porto Alegre, a teaching hospital in Brazil, to compare the efficacy of morning and evening administration of LT4 for hypothyroidism control in older patients. The study protocol is published elsewhere. A total of 201 participants, ≥60 years old, with primary hypothyroidism treated with LT4 for at least 6 months and on stable doses for at least 3 months were included. Participants were randomly assigned to a starting group of morning LT4 intake (60 min before breakfast) or bedtime LT4 intake (60 min after the last meal). After ≥12 weeks of follow-up, a crossover between strategies was performed. The primary outcome was the change in serum thyrotropin (Thyroid-Stimulating Hormone; TSH) levels after 12 weeks of each LT4 administration regimen.ResultsA total of 201 participants with mean age of 72.4 ± 7.2 years were included, out of which 84.1% were women; baseline characteristics and frequency of controlled hypothyroidism were similar between groups. Mean baseline TSH was 3.43 ± 0.25 mUI/L. In total, 118 participants attended three meetings, allowing 135 comparisons by crossover analytic strategy. Mean TSH levels after follow-up were 2.95 ± 2.86 in the morning group and 3.64 ± 2.86 in the bedtime group, p = 0.107.DiscussionThyroid-Stimulating Hormone levels and frequency of controlled hypothyroidism were similar during the follow-up period regardless of the treatment regimen (morning or bedtime).

Project description:Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P?0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P<0.001) and post (AM: 98.0±9.0, PM: 52.7±6.0 ng/ml, P<0.001) exercise. Interestingly, individual cortisol differences pre vs post exercise indicate a time-of-day effect (AM difference: -2±2.6%, PM difference: 14.0±6.7%, P = 0.03). A time-of-day related elevation in serum IGFBP-3 (AM: 3274.9 ± 345.2, PM: 3605.1 ± 367.5, p = 0.032) was also evident. Pre exercise myogenic index (AM: 8.0±0.6%, PM: 16.8±1.1%) and myotube width (AM: 48.0±3.0, PM: 71.6±1.9 ?m) were significantly elevated (P<0.001) in the evening. Post exercise myogenic index was greater AM (11.5±1.6%) compared with PM (4.6±0.9%). No difference was observed in myotube width (AM: 48.5±1.5, PM: 47.8±1.8 ?m) (P>0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely.

Project description:Binge alcohol consumption elicits acute and robust increases of muscle sympathetic nerve activity (MSNA), yet the impact of evening binge drinking on morning-after MSNA is unknown. The present study examined the effects of evening binge alcohol consumption on polysomnographic sleep and morning-after MSNA. We hypothesized that evening binge drinking (i.e. 4-5 drink equivalent in <2 h) would reduce sleep quality and increase morning-after blood pressure (BP) and MSNA. Following a familiarization night within the sleep laboratory, 22 participants (12 men, 10 women; 25 ± 1 yr) were examined after simulated binge drinking or fluid control (randomized, crossover design). Morning MSNA was successfully recorded across both conditions in 16 participants (8 men, 8 women) during a 10-min baseline and three Valsalva's maneuvers (VM). Binge drinking reduced rapid eye movement (REM) sleep (15 ± 1 vs. 20 ± 1%, P = 0.003), increased stage II sleep (54 ± 1 vs. 51 ± 1%, P = 0.002), and increased total urine output (2.9 ± 0.2 vs. 2.1 ± 0.1 liters, P < 0.001) but did not alter morning-after urine specific gravity. Binge drinking increased morning-after heart rate [65 (54-72) vs. 58 (51-67) beats/min, P = 0.013] but not resting BP or MSNA. Binge drinking elicited greater sympathoexcitation during VM (38 ± 3 vs. 43 ± 3 bursts/min, P = 0.036). Binge drinking augmented heart rate (P = 0.002), systolic BP (P = 0.022), and diastolic BP (P = 0.037) reactivity to VM phase IV and blunted cardiovagal baroreflex sensitivity during VM phases II (P = 0.028) and IV (P = 0.043). In conclusion, evening binge alcohol consumption disrupted REM sleep and morning-after autonomic function. These findings provide new mechanistic insight into the potential role of binge drinking on cardiovascular risk.NEW & NOTEWORTHY Chronic binge alcohol consumption is associated with future cardiovascular disease (CVD) risk in both men and women. In addition, binge alcohol consumption is known to disrupt normal sleep quality during the early morning hours, coinciding with the morning sympathetic surge. In the present study, an evening of binge alcohol consumption increased baseline morning heart rate and cardiovascular reactivity during the Valsalva maneuver (VM) strain. Specifically, muscle sympathetic nerve activity and phase IV hemodynamic responses increased during VM the morning after binge alcohol consumption. The autonomic dysfunction and increased cardiovascular reactivity during VM suggests a contributing mechanism to CVD risk present in individuals who binge drink.

Dataset Information

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

Publications

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

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