The Preventative Role of Exogenous Melatonin Administration in Patients With Advanced Cancer Who Are at Risk of Delirium: a Feasibility Study

Bruyere Research Institute

Status and phase: Completed; Phase 2

Conditions: Cancer

Treatments: Other: Placebo; Other: Melatonin

Study type: Interventional

Funder types: Other

Identifiers

NCT02200172

BRI-MELAT-2013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

60 participants in 2 patient groups, including a placebo group

Melatonin

Active Comparator group

Description:

A single daily sublingually administered tablet of 3mg non-animal synthetic source melatonin (immediate-release) 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.

Treatment:

Other: Melatonin

Placebo

Placebo Comparator group

Description:

A single daily sublingually administered tablet of 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.

Treatment:

Other: Placebo