The preventative role of exogenous melatonin administration to patients with advanced cancer who are at risk of delirium: study protocol for a randomized controlled trial

Abstract

BackgroundDelirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer.Methods/DesignAdult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission.DiscussionThe outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer.Trial registrationRegistered with ClinicalTrials.gov: NCT02200172 Registered on 21 July 2014.Health Canada protocol number: BRI-MELAT-2013 (Final approved protocol version (Version 3): 18 June 2014) (Notice of Amended Authorization (NOA) received 14 November 2014).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1525-8) contains supplementary material, which is available to authorized users.

Promising Antineoplastic Actions of Melatonin

“…Another important beneficial action of melatonin is its ability to reduce chemotherapy and radiotherapy-induced toxicity and oxidative stress. Melatonin has also been reported to be useful in the treatment of the associated insomnia, cachexia, delirium, and other symptoms that often occur in cancer patients ( Mahmoud et al, 2005 ; Davis and Goforth, 2014 ; da Silva et al, 2015 ; Bush et al, 2016 ; Waldman et al, 2016 ). There are also some studies that showed that melatonin has weak or no antineoplastic palliative effect ( Del Fabbro et al, 2013 ; Lund Rasmussen et al, 2015 ).…”

Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

“…In addition, melatonin is an anticancer hormone and a potential target for cancer treatments (12). Several studies have revealed that melatonin is useful for the prevention of cancer (13,14). The antitumor ability of melatonin may be mediated by numerous mechanisms, including the activation of antioxidative stress, inhibition of migration and induction of apoptosis (15)(16)(17).…”

Melatonin and the Prevention and Management of Delirium: A Scoping Study

“…Future RCTs will need to include well-validated tools to identify delirium and ensure they are adequately powered to identify between-group differences. A number of published study protocols ( 59 , 60 ), including feasibility studies ( 61 , 62 ), suggest that such improvements in the available evidence of the efficacy of melatonin analogs to prevent delirium are forthcoming.…”