title: 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: Delirium 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.
  
  
  
  Adult 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.
  
  
  
  The 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.
  
  
  
  Registered 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).
authors: Division of Palliative Care, Department of Medicine, University of Ottawa, 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada. sbush@bruyere.org.|Bruyère Research Institute (BRI), 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada. sbush@bruyere.org.|Ottawa Hospital Research Institute (OHRI), 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada. sbush@bruyere.org.|Bruyère Continuing Care, 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada. sbush@bruyere.org.
authors: Shirley Harvey
authors: SH
authors: Bush
authors: Ottawa Hospital Research Institute (OHRI), 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.
authors: Nathalie
authors: N
authors: Lacaze-Masmonteil
authors: Bruyère Research Institute (BRI), 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada.
authors: Marie Theresa
authors: MT
authors: McNamara-Kilian
authors: Bruyère Research Institute (BRI), 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada.
authors: Alistair Richard
authors: AR
authors: MacDonald
authors: Bruyère Continuing Care, 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada.
authors: Sallyanne
authors: S
authors: Tierney
authors: Ottawa Hospital Research Institute (OHRI), 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.|Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, K1H 5B2, Canada.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Centre for Practice-Changing Research (CPCR), 501 Smyth Road, Room L1231, Box 201B, Ottawa, Ontario, K1H 8L6, Canada.
authors: Franco
authors: F
authors: Momoli
authors: Centre of Cardiovascular and Chronic Care, Faculty of Health, University of Technology Sydney, Level 3, 235 Jones Street, Ultimo, NSW, 2007, Australia.
authors: Meera
authors: M
authors: Agar
authors: Discipline, Palliative and Supportive Services, Bedford Park, Flinders University, Adelaide, SA, Australia.
authors: David Christopher
authors: DC
authors: Currow
authors: Division of Palliative Care, Department of Medicine, University of Ottawa, 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada.|Bruyère Research Institute (BRI), 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada.|Ottawa Hospital Research Institute (OHRI), 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.|Bruyère Continuing Care, 43 Bruyère Street, Ottawa, ON, K1N 5C8, Canada.
authors: Peter Gerard
authors: PG
authors: Lawlor
mesh_terms: D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D003704:Dementia / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D004311:Double-Blind Method; D005240:Feasibility Studies; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D009864:Ontario; D010166:Palliative Care; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002491:Central Nervous System Agents; D008550:Melatonin
keywords: Advanced cancer; Delirium; Feasibility study; Melatonin; Pilot; Prevention; Randomized controlled trial (RCT); Sleep