The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial

Madsen, Michael Tvilling; Isbrand, Anders; Andersen, Ulrik B.; Andersen, Lotte Bøgh; Taskiran, Mustafa; Simonsen, Erik; Gögenur, Ismail

doi:10.1186/s13063-017-1806-x

Cited by 23 publications

(18 citation statements)

References 76 publications

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“…It was performed as a sub‐study to the MEDACIS trial, registered on clinicaltrails.gov (Identifier: NCT02451293), GCP monitored, and received all required approvals. The inclusion and exclusion criteria followed MEDACIS . Moreover, patients with conditions that precluded ED measurements, such as having only one arm, were excluded.…”

Section: Methodsmentioning

confidence: 99%

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The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial

Zahid

Isbrand

Kleif

et al. 2019

Journal of Pineal Research

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Endothelial dysfunction (ED) precedes acute coronary syndrome. Oxidative stress results in ED but is reversible. Melatonin is aside from being a circadian hormone, also an antioxidant. The aim of this study was to investigate whether 25 mg melatonin administered for twelve weeks following acute coronary syndrome (ACS) could improve ED. In this placebo‐controlled randomized trial, ED was measured as reactive hyperemia index (RHI) at baseline, day 14, and day 84. The effect was assessed using a generalized estimating equation adjusted for the baseline RHI. As secondary outcome, the concentrations of three biomarkers were measured: l‐arginine, asymmetric dimethylarginine, and uric acid. Thirty‐one patients were included in the study. The intention‐to‐treat analysis of the primary outcome had 26 patients due to missing data. The estimated marginal mean difference in RHI at day 14 and day 84 between the groups was 0.15 (95% CI: 0.29‐0.01, P = .039) in favor of the placebo group. No significant differences in the biomarker concentrations were found. Melatonin treatment after ACS did not improve but may have aggravated ED. The significant difference between groups was in favor of placebo, but this might be due to the effect of missing data or uneven distribution of comorbidities.

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Section: Methodsmentioning

confidence: 99%

“…The inclusion and exclusion criteria followed MEDACIS. 9 Moreover, patients with conditions that precluded ED measurements, such as having only one arm, were excluded. Participants received a box containing 25 mg melatonin or matching placebo at baseline, which were indistinguishable.…”

Section: Methodsmentioning

confidence: 99%

The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial

Zahid

Isbrand

Kleif

et al. 2019

Journal of Pineal Research

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“…Completed trial on prophylactic melatonin treatment for preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following acute coronary syndrome (Clinical trials: NCT02451293) [20].…”

Section: Clinical Trials With Melatonin In Heart Diseasesmentioning

confidence: 99%

Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use

Baltatu

Senar²,

Campos

et al. 2019

IJMS

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In this review we summarized the actual clinical data for a cardioprotective therapeutic role of melatonin, listed melatonin and its agonists in different stages of development, and evaluated the melatonin cardiovascular target tractability and prediction using machine learning on ChEMBL. To date, most clinical trials investigating a cardioprotective therapeutic role of melatonin are in phase 2a. Selective melatonin receptor agonists Tasimelteon, Ramelteon, and combined melatonergic-serotonin Agomelatine, and other agonists with registered structures in CHEMBL were not yet investigated as cardioprotective or cardiovascular drugs. As drug-able for these therapeutic targets, melatonin receptor agonists have the benefit over melatonin of well-characterized pharmacologic profiles and extensive safety data. Recent reports of the X-ray crystal structures of MT1 and MT2 receptors shall lead to the development of highly selective melatonin receptor agonists. Predictive models using machine learning could help to identify cardiovascular targets for melatonin. Selecting ChEMBL scores > 4.5 in cardiovascular assays, and melatonin scores > 4, we obtained 284 records from 162 cardiovascular assays carried out with 80 molecules with predicted or measured melatonin activity. Melatonin activities (agonistic or antagonistic) found in these experimental cardiovascular assays and models include arrhythmias, coronary and large vessel contractility, and hypertension. Preclinical proof-of-concept and early clinical studies (phase 2a) suggest a cardioprotective benefit from melatonin in various heart diseases. However, larger phase 3 randomized interventional studies are necessary to establish melatonin and its agonists’ actions as cardioprotective therapeutic agents.

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“…These antidepressant-like effects of melatonin have been associated with neurotransmitter systems, such as the serotoninergic, glutamatergic, and GABAergic systems, along with hypothalamic–pituitary–adrenal axis modulation [ 269 , 271 , 272 ]. The antidepressant effects of melatonin remain unclear in human studies, although several studies have reported that melatonin use is beneficial for improving symptoms associated with depression [ 274 , 275 ].…”

Section: Melatonin and Depressionmentioning

confidence: 99%

Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

Won

Lee

Kim

2021

IJMS

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Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers.

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The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial

Cited by 23 publications

References 76 publications

The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial

The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial

Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use

Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

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