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

NCT ID: NCT02200172

Last Updated: 2016-07-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2016-04-30

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.

Conditions

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Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Melatonin

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.

Group Type ACTIVE_COMPARATOR

Melatonin

Intervention Type OTHER

Sublingual 3mg non-animal synthetic source melatonin daily at 21.00 hours (±1 hour).

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Interventions

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Melatonin

Sublingual 3mg non-animal synthetic source melatonin daily at 21.00 hours (±1 hour).

Intervention Type OTHER

Placebo

Intervention Type OTHER

Other Intervention Names

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Sublingual placebo daily at 21.00 hours (±1 hour).

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bruyère Health Research Institute.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Lawlor, MB, MMedSc

Role: PRINCIPAL_INVESTIGATOR

Clinician Scientist, Bruyère Research Institute; Medical Director, Bruyère Continuing Care

Locations

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Bruyère Continuing Care

Ottawa, Ontario, Canada

Site Status

Countries

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Canada

References

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Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg. 2002 Feb;94(2):338-9, table of contents. doi: 10.1097/00000539-200202000-00019.

Reference Type BACKGROUND
PMID: 11812694 (View on PubMed)

Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2011 Jul;26(7):687-94. doi: 10.1002/gps.2582. Epub 2010 Sep 15.

Reference Type BACKGROUND
PMID: 20845391 (View on PubMed)

Hagen NA, Biondo PD, Brasher PM, Stiles CR. Formal feasibility studies in palliative care: why they are important and how to conduct them. J Pain Symptom Manage. 2011 Aug;42(2):278-89. doi: 10.1016/j.jpainsymman.2010.11.015. Epub 2011 Mar 27.

Reference Type BACKGROUND
PMID: 21444184 (View on PubMed)

Siddiqi N, Stockdale R, Britton AM, Holmes J. Interventions for preventing delirium in hospitalised patients. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005563. doi: 10.1002/14651858.CD005563.pub2.

Reference Type BACKGROUND
PMID: 17443600 (View on PubMed)

Tabet N, Howard R. Pharmacological treatment for the prevention of delirium: review of current evidence. Int J Geriatr Psychiatry. 2009 Oct;24(10):1037-44. doi: 10.1002/gps.2220.

Reference Type BACKGROUND
PMID: 19226527 (View on PubMed)

Agar M, Lawlor P. Delirium in cancer patients: a focus on treatment-induced psychopathology. Curr Opin Oncol. 2008 Jul;20(4):360-6. doi: 10.1097/CCO.0b013e328302167d.

Reference Type BACKGROUND
PMID: 18525328 (View on PubMed)

Lawlor PG, Fainsinger RL, Bruera ED. Delirium at the end of life: critical issues in clinical practice and research. JAMA. 2000 Nov 15;284(19):2427-9. doi: 10.1001/jama.284.19.2427. No abstract available.

Reference Type BACKGROUND
PMID: 11074759 (View on PubMed)

Miyazaki T, Kuwano H, Kato H, Ando H, Kimura H, Inose T, Ohno T, Suzuki M, Nakajima M, Manda R, Fukuchi M, Tsukada K. Correlation between serum melatonin circadian rhythm and intensive care unit psychosis after thoracic esophagectomy. Surgery. 2003 Jun;133(6):662-8. doi: 10.1067/msy.2003.149.

Reference Type BACKGROUND
PMID: 12796735 (View on PubMed)

Olofsson K, Alling C, Lundberg D, Malmros C. Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients. Acta Anaesthesiol Scand. 2004 Jul;48(6):679-84. doi: 10.1111/j.0001-5172.2004.00401.x.

Reference Type BACKGROUND
PMID: 15196098 (View on PubMed)

de Jonghe A, van Munster BC, van Oosten HE, Goslings JC, Kloen P, van Rees C, Wolvius R, van Velde R, Levi MM, Korevaar JC, de Rooij SE; Amsterdam Delirium Study group. The effects of melatonin versus placebo on delirium in hip fracture patients: study protocol of a randomised, placebo-controlled, double blind trial. BMC Geriatr. 2011 Jul 5;11:34. doi: 10.1186/1471-2318-11-34.

Reference Type BACKGROUND
PMID: 21729284 (View on PubMed)

de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry. 2010 Dec;25(12):1201-8. doi: 10.1002/gps.2454.

Reference Type BACKGROUND
PMID: 21086534 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33087111 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27515515 (View on PubMed)

Related Links

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http://www.bruyere.org/en/our-institute

Bruyère Research Institute, Ottawa, Canada

Other Identifiers

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BRI-MELAT-2013

Identifier Type: -

Identifier Source: org_study_id

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