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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02200172
• Other study ID #: BRI-MELAT-2013
• Status: Completed
• Phase: Phase 2
• First received: July 21, 2014
• Last updated: July 18, 2016
• Start date: December 2014
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: Bruyere Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cancer
• Delirium

Intervention

Other:
• Melatonin
Sublingual 3mg non-animal synthetic source melatonin daily at 21.00 hours (±1 hour).
• Placebo

Locations

Country	Name	City	State
Canada	Bruyère Continuing Care	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Bruyere Research Institute

Country where clinical trial is conducted

Canada, 

References & Publications (11)

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. Review. — View Citation

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. Erratum in: Int J Geriatr Psychiatry. 2014 May;29(5):550. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg. 2002 Feb;94(2):338-9, table of contents. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Siddiqi N, Stockdale R, Britton AM, Holmes J. Interventions for preventing delirium in hospitalised patients. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005563. Review. Update in: Cochrane Database Syst Rev. 2016;3:CD005563. — View Citation

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. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Number of times the blinding on the trial product is broken.	This number will indicate any further need for research team training.	8 months	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	Yes

External Links

•   Bruyère Research Institute, Ottawa, Canada