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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cancer

Intervention / Treatment
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* Other: Melatonin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Melatonin<br>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. | Other: Melatonin<br>* Sublingual 3mg non-animal synthetic source melatonin daily at 21.00 hours (±1 hour).<br>|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br> <br> * Other names: Sublingual placebo daily at 21.00 hours (±1 hour).;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first onset of delirium for participants receiving active comparator versus placebo | Preliminary data will help determine the appropriateness of this outcome measure in a larger trial. | 8 months | 
| Number of times the blinding on the trial product is broken. | This number will indicate any further need for research team training. | 8 months | 
| Recruitment and retention rates | Recruitment and retention rates will determine if a larger trial with the same design will allow for a sufficient number of participants. | 8 months | 
| Frequency of protocol violation | The frequency of protocol violations will indicate if a larger trial with the same design can be implemented in a palliative care setting or require modification. | 8 months | 
| Number of unsolicited positive versus negative comments from participants, families, and Palliative Care Unit staff | Comments that are voluntarily provided will show whether the trial is acceptable to participants, families, Palliative Care Unit staff. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predisposing and precipitating risks form completion rate | Predisposing and precipitating factors will be collected on trial forms throughout the trial. The feasibility of collecting this data on the Palliative Care Unit will be measured by form completion rates. | 8 months | 
| Number of participants with serious adverse events related to the active comparator | To assess the safety of the proposed intervention in this palliative care population will be assessed on an ongoing basis. | Participants will be followed for the duration of trial product administration plus 2 days for an expected total of 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Melatonin, Delirium, Feasibility Studies, Palliative Care