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

NCT02200172 | Completed Phase 2 DMC

• 1 other identifier: BRI-MELAT-2013
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer

Keywords

Cancer; Melatonin; Delirium; Feasibility Studies; Palliative Care

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (2)

• Predisposing and precipitating risks form completion rate

  8 months

• Number of participants with serious adverse events related to the active comparator

  Participants will be followed for the duration of trial product administration plus 2 days for an expected total of 30 days

Study Arms (2)

Melatonin

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Melatonin OTHER

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

Melatonin

Placebo OTHER

Also known as: Sublingual placebo daily at 21.00 hours (±1 hour).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bruyère Health Research Institute.: lead

Study Sites (1)

Bruyère Continuing Care

Ottawa, Ontario, K1N 5C8, Canada

Location

Related Publications (13)

• 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.

  PMID: 11812694 BACKGROUND

• 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.

  PMID: 20845391 BACKGROUND

• 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.

  PMID: 21444184 BACKGROUND

• 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.

  PMID: 17443600 BACKGROUND

• 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.

  PMID: 19226527 BACKGROUND

• 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.

  PMID: 18525328 BACKGROUND

• 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.

  PMID: 11074759 BACKGROUND

• 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.

  PMID: 12796735 BACKGROUND

• 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.

  PMID: 15196098 BACKGROUND

• 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.

  PMID: 21729284 BACKGROUND

• 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.

  PMID: 21086534 BACKGROUND

• 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.

  PMID: 33087111 DERIVED

• 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.

  PMID: 27515515 DERIVED

Related Links

• Bruyère Research Institute, Ottawa, Canada

MeSH Terms

Conditions

Neoplasms; Delirium

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Peter Lawlor, MB, MMedSc

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 25, 2014
• Study Start: December 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 19, 2016

Record last verified: 2016-07

Locations

CA (1)