Clinical trial NCT02200172: The Preventative Role of Exogenous Melatonin Administration in Patients With Advanced Cancer Who Are at Risk of Delirium: a Feasibility Study
Official title: The Preventative Role of Exogenous Melatonin Administration in Patients With Advanced Cancer Who Are at Risk of Delirium: a Feasibility Study Prior to a Larger Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: Cancer
Melatonin
Delirium
Feasibility Studies
Palliative Care
Lead sponsor: Bruyere Research Institute
Sponsor class: OTHER
First posted: 2014-07-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this feasibility study is to inform a larger randomized, placebo-controlled, double blind, parallel-group, single-centre trial of an oral, daily administered single dose of melatonin to prevent delirium in patients with advanced cancer.

Detailed description: Delirium is a very common and distressing neuropsychiatric syndrome in palliative care and a variety of other settings. It is associated with increases in morbidity, mortality, health care costs and most importantly in levels of patient and family distress. Inpatient palliative care is delivered in stand-alone hospice units and increasingly in designated units in acute care hospitals, where delirium occurrence rates of over 80% have been reported in the last hours and days before death. Most patients in these units have a cancer diagnosis. Given the increasing elderly proportion of the population, and that cancer is predominantly a disease of the elderly, there is a pivotal need to develop primary, secondary and tertiary preventative strategies for delirium in these patients.

Although sleep-wake cycle disturbance is not a core diagnostic criterion for delirium, studies of delirium in cancer patients have reported occurrence rates of 75-100%. This most likely reflects a circadian rhythm disturbance. Recent research suggests that giving melatonin to patients who are admitted to hospital may prevent them from developing delirium.

This feasibility study aims to inform a larger randomized, placebo-controlled, double blind, parallel-group, single-centre trial of an oral, daily administered single dose of melatonin to prevent delirium in patients with advanced cancer.

The study will be conducted on the 31-bed Palliative Care Unit (PCU), a university teaching unit, at Bruyère Continuing Care. The intervention consists of a single daily sublingually administered tablet of either 3mg non-animal synthetic source or placebo at 21.00 hours (±1 hour), starting on study day 1 and stopping on study day 28 of admission or earlier in the event of death or discharge. The study drug will be discontinued immediately if incident delirium occurs before day 28.

Throughout the trial, multiple dimensions of feasibility will be evaluated such as recruitment, retention and acceptability of study procedures.

Eligibility criteria: Inclusion Criteria:

* Males and females ≥ 18 years
* Cancer diagnosis
* Admitted to Palliative Care Unit
* English speaking
* Cognitive capacity to give informed consent or substitute decision maker is accessible to provide consent
* Palliative Performance Scale ≥ 30% at the time of consent

Exclusion Criteria:

* Delirium present on admission (assessed clinically with the CAM)
* Known psychotic disorder other than dementia
* Inability to take medications sublingually or via gastrostomy tube
* Known allergy to melatonin or placebo content
* Use of melatonin within the two weeks preceding admission
* Patient on warfarin treatment or other oral anticoagulant
* Communication problems that cannot be accommodated, including deafness, tracheostomy, aphasia, dysarthria or emotional distress
* On other investigational agents or treatments
* Pregnancy or lactation
* Severe visual impairment or designated legally blind
* Immunosuppressant medication use in the context of autoimmune disease or post organ transplantation

Primary outcomes:
measure: Time to first onset of delirium for participants receiving active comparator versus placebo
timeFrame: 8 months
measure: Number of times the blinding on the trial product is broken.
timeFrame: 8 months
measure: Recruitment and retention rates
timeFrame: 8 months
measure: Frequency of protocol violation
timeFrame: 8 months
measure: Number of unsolicited positive versus negative comments from participants, families, and Palliative Care Unit staff
timeFrame: 8 months
Secondary outcomes:
measure: Predisposing and precipitating risks form completion rate
timeFrame: 8 months
measure: Number of participants with serious adverse events related to the active comparator
timeFrame: Participants will be followed for the duration of trial product administration plus 2 days for an expected total of 30 days
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Bruyère Continuing Care
state: Ontario
Study officials:
affiliation: Clinician Scientist, Bruyère Research Institute; Medical Director, Bruyère Continuing Care
name: Peter Lawlor, MB, MMedSc
role: PRINCIPAL_INVESTIGATOR
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citation: Lawlor PG, McNamara-Kilian MT, MacDonald AR, Momoli F, Tierney S, Lacaze-Masmonteil N, Dasgupta M, Agar M, Pereira JL, Currow DC, Bush SH. Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial. BMC Palliat Care. 2020 Oct 21;19(1):163. doi: 10.1186/s12904-020-00669-z.
citation: Bush SH, Lacaze-Masmonteil N, McNamara-Kilian MT, MacDonald AR, Tierney S, Momoli F, Agar M, Currow DC, Lawlor PG. 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. Trials. 2016 Aug 11;17:399. doi: 10.1186/s13063-016-1525-8.