<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02200172</url>
  </required_header>
  <id_info>
    <org_study_id>BRI-MELAT-2013</org_study_id>
    <nct_id>NCT02200172</nct_id>
  </id_info>
  <brief_title>The Preventative Role of Exogenous Melatonin Administration in Patients With Advanced Cancer Who Are at Risk of Delirium: a Feasibility Study</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bruyere Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bruyere Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this feasibility study is to inform a larger randomized, placebo-controlled,&#xD;
      double blind, parallel-group, single-centre trial of an oral, daily administered single dose&#xD;
      of melatonin to prevent delirium in patients with advanced cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Delirium is a very common and distressing neuropsychiatric syndrome in palliative care and a&#xD;
      variety of other settings. It is associated with increases in morbidity, mortality, health&#xD;
      care costs and most importantly in levels of patient and family distress. Inpatient&#xD;
      palliative care is delivered in stand-alone hospice units and increasingly in designated&#xD;
      units in acute care hospitals, where delirium occurrence rates of over 80% have been reported&#xD;
      in the last hours and days before death. Most patients in these units have a cancer&#xD;
      diagnosis. Given the increasing elderly proportion of the population, and that cancer is&#xD;
      predominantly a disease of the elderly, there is a pivotal need to develop primary, secondary&#xD;
      and tertiary preventative strategies for delirium in these patients.&#xD;
&#xD;
      Although sleep-wake cycle disturbance is not a core diagnostic criterion for delirium,&#xD;
      studies of delirium in cancer patients have reported occurrence rates of 75-100%. This most&#xD;
      likely reflects a circadian rhythm disturbance. Recent research suggests that giving&#xD;
      melatonin to patients who are admitted to hospital may prevent them from developing delirium.&#xD;
&#xD;
      This feasibility study aims to inform a larger randomized, placebo-controlled, double blind,&#xD;
      parallel-group, single-centre trial of an oral, daily administered single dose of melatonin&#xD;
      to prevent delirium in patients with advanced cancer.&#xD;
&#xD;
      The study will be conducted on the 31-bed Palliative Care Unit (PCU), a university teaching&#xD;
      unit, at Bruyère Continuing Care. The intervention consists of a single daily sublingually&#xD;
      administered tablet of either 3mg non-animal synthetic source or placebo at 21.00 hours (±1&#xD;
      hour), starting on study day 1 and stopping on study day 28 of admission or earlier in the&#xD;
      event of death or discharge. The study drug will be discontinued immediately if incident&#xD;
      delirium occurs before day 28.&#xD;
&#xD;
      Throughout the trial, multiple dimensions of feasibility will be evaluated such as&#xD;
      recruitment, retention and acceptability of study procedures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to first onset of delirium for participants receiving active comparator versus placebo</measure>
    <time_frame>8 months</time_frame>
    <description>Preliminary data will help determine the appropriateness of this outcome measure in a larger trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of times the blinding on the trial product is broken.</measure>
    <time_frame>8 months</time_frame>
    <description>This number will indicate any further need for research team training.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recruitment and retention rates</measure>
    <time_frame>8 months</time_frame>
    <description>Recruitment and retention rates will determine if a larger trial with the same design will allow for a sufficient number of participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of protocol violation</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of unsolicited positive versus negative comments from participants, families, and Palliative Care Unit staff</measure>
    <time_frame>8 months</time_frame>
    <description>Comments that are voluntarily provided will show whether the trial is acceptable to participants, families, Palliative Care Unit staff.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Predisposing and precipitating risks form completion rate</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with serious adverse events related to the active comparator</measure>
    <time_frame>Participants will be followed for the duration of trial product administration plus 2 days for an expected total of 30 days</time_frame>
    <description>To assess the safety of the proposed intervention in this palliative care population will be assessed on an ongoing basis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <description>Sublingual 3mg non-animal synthetic source melatonin daily at 21.00 hours (±1 hour).</description>
    <arm_group_label>Melatonin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sublingual placebo daily at 21.00 hours (±1 hour).</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females ≥ 18 years&#xD;
&#xD;
          -  Cancer diagnosis&#xD;
&#xD;
          -  Admitted to Palliative Care Unit&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
          -  Cognitive capacity to give informed consent or substitute decision maker is accessible&#xD;
             to provide consent&#xD;
&#xD;
          -  Palliative Performance Scale ≥ 30% at the time of consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Delirium present on admission (assessed clinically with the CAM)&#xD;
&#xD;
          -  Known psychotic disorder other than dementia&#xD;
&#xD;
          -  Inability to take medications sublingually or via gastrostomy tube&#xD;
&#xD;
          -  Known allergy to melatonin or placebo content&#xD;
&#xD;
          -  Use of melatonin within the two weeks preceding admission&#xD;
&#xD;
          -  Patient on warfarin treatment or other oral anticoagulant&#xD;
&#xD;
          -  Communication problems that cannot be accommodated, including deafness, tracheostomy,&#xD;
             aphasia, dysarthria or emotional distress&#xD;
&#xD;
          -  On other investigational agents or treatments&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Severe visual impairment or designated legally blind&#xD;
&#xD;
          -  Immunosuppressant medication use in the context of autoimmune disease or post organ&#xD;
             transplantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Lawlor, MB, MMedSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinician Scientist, Bruyère Research Institute; Medical Director, Bruyère Continuing Care</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bruyère Continuing Care</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1N 5C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.bruyere.org/en/our-institute</url>
    <description>Bruyère Research Institute, Ottawa, Canada</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>11812694</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20845391</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21444184</PMID>
  </reference>
  <reference>
    <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. doi: 10.1002/14651858.CD005563.pub2.</citation>
    <PMID>17443600</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19226527</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>18525328</PMID>
  </reference>
  <reference>
    <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. doi: 10.1001/jama.284.19.2427. No abstract available.</citation>
    <PMID>11074759</PMID>
  </reference>
  <reference>
    <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. doi: 10.1067/msy.2003.149.</citation>
    <PMID>12796735</PMID>
  </reference>
  <reference>
    <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. doi: 10.1111/j.0001-5172.2004.00401.x.</citation>
    <PMID>15196098</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21729284</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21086534</PMID>
  </reference>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>July 18, 2016</last_update_submitted>
  <last_update_submitted_qc>July 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Melatonin</keyword>
  <keyword>Delirium</keyword>
  <keyword>Feasibility Studies</keyword>
  <keyword>Palliative Care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02200172
org study id: BRI-MELAT-2013
nct id: NCT02200172
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to first onset of delirium for participants receiving active comparator versus placebo
time frame: 8 months
description: Preliminary data will help determine the appropriateness of this outcome measure in a larger trial.
measure: Number of times the blinding on the trial product is broken.
time frame: 8 months
description: This number will indicate any further need for research team training.
measure: Recruitment and retention rates
time frame: 8 months
description: Recruitment and retention rates will determine if a larger trial with the same design will allow for a sufficient number of participants.
measure: Frequency of protocol violation
time frame: 8 months
description: 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.
measure: Number of unsolicited positive versus negative comments from participants, families, and Palliative Care Unit staff
time frame: 8 months
description: Comments that are voluntarily provided will show whether the trial is acceptable to participants, families, Palliative Care Unit staff.
measure: Predisposing and precipitating risks form completion rate
time frame: 8 months
description: 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.
measure: Number of participants with serious adverse events related to the active comparator
time frame: Participants will be followed for the duration of trial product administration plus 2 days for an expected total of 30 days
description: To assess the safety of the proposed intervention in this palliative care population will be assessed on an ongoing basis.
arm group label: Melatonin
arm group type: Active Comparator
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.
arm group label: Placebo
arm group type: Placebo Comparator
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.
intervention type: Other
intervention name: Melatonin
description: Sublingual 3mg non-animal synthetic source melatonin daily at 21.00 hours (±1 hour).
arm group label: Melatonin
intervention type: Other
intervention name: Placebo
arm group label: Placebo
other name: Sublingual placebo daily at 21.00 hours (±1 hour).
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter Lawlor, MB, MMedSc
role: Principal Investigator
affiliation: Clinician Scientist, Bruyère Research Institute; Medical Director, Bruyère Continuing Care
facility: 
country: Canada
url: http://www.bruyere.org/en/our-institute
description: Bruyère Research Institute, Ottawa, Canada
citation: 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
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.
PMID: 20845391
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.
PMID: 21444184
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. doi: 10.1002/14651858.CD005563.pub2.
PMID: 17443600
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.
PMID: 19226527
citation: 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
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. doi: 10.1001/jama.284.19.2427. No abstract available.
PMID: 11074759
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. doi: 10.1067/msy.2003.149.
PMID: 12796735
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. doi: 10.1111/j.0001-5172.2004.00401.x.
PMID: 15196098
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.
PMID: 21729284
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.
PMID: 21086534
responsible party type: Sponsor
mesh term: Delirium
mesh term: Melatonin