<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/NCT03785938</url>
  </required_header>
  <id_info>
    <org_study_id>IRAS PROJECT ID: 246313</org_study_id>
    <nct_id>NCT03785938</nct_id>
  </id_info>
  <brief_title>Mucositis and Infection Reduction With Liquid Probiotics in Children With Cancer</brief_title>
  <acronym>MaCROS</acronym>
  <official_title>Mucositis and Infection Reduction With Liquid Probiotics in Children With Cancer: a Randomised-controlled Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Leeds</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Leeds</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate the feasibility of an randomised-controlled trial to&#xD;
      investigate the efficacy of liquid probiotics to prevent or reduce mucositis and infection in&#xD;
      children diagnosed with cancer who are undergoing treatment with regimes likely to cause&#xD;
      mucositis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TRIAL DESIGN&#xD;
&#xD;
      This will be a single-centre double-blind randomised-controlled feasibility study.&#xD;
&#xD;
      TRIAL SETTING&#xD;
&#xD;
      This study will take place at Leeds Teaching Hospital Trust (LTHT), Leeds UK. Participants&#xD;
      will be approached whilst admitted as inpatients (typically the paediatric haematology&#xD;
      oncology wards) and during outpatient clinics.&#xD;
&#xD;
      METHOD&#xD;
&#xD;
      Allocation sequence from a randomisation schedule will be generated A screening or trial ID&#xD;
      number will be assigned to each participant.&#xD;
&#xD;
      The allocation sequence will be concealed from health care professionals, participants and&#xD;
      families. Only the pharmacy team involved in randomisation, allocation will not be blinded to&#xD;
      allocation sequence and generation.&#xD;
&#xD;
      Following identification, confirmation of eligibility, consent and allocation of trial ID of&#xD;
      the participant, a prescription will be produced and the probiotic or placebo will be&#xD;
      allocated accordingly.&#xD;
&#xD;
      Appearance of the intervention and placebo will be similar in appearance, smell and taste.&#xD;
      The placebo will include maltdextrin (a polysaccharide). Both the probiotic and placebo will&#xD;
      be produced by the company Symprove.&#xD;
&#xD;
      Participants will start the course of probiotic or placebo on the first day of their course&#xD;
      of chemotherapy orally, or using an nasogastric or gastrostomy tube and will continue this&#xD;
      for 14 days. Doses will be adjusted according to the age of the participant as follows:&#xD;
&#xD;
      1-4 years:20ml once a day 4-11 years: 0.5ml/kg once a day 12-18 years: 1ml/kg once a day&#xD;
      Placebo will be delivered in similar, packaging, appearance and taste.&#xD;
&#xD;
      Participants or their parents will be asked to fill in a diary (paper or electronic using a&#xD;
      web-app) daily for 21 days in total. The diary will include questions to assess nausea,&#xD;
      vomiting, diarrhoea, pain and oral mucositis. An example of the patient diaries offered is&#xD;
      supplied. Either the participant or parent will fill in the diary on a daily basis for a&#xD;
      minimum of 21 days.&#xD;
&#xD;
      The web-app is an electronic version of the paper diary. Participants will to chose their&#xD;
      preferred method. Participants will be given the URL which they can download onto their phone&#xD;
      as a web-app. Data provided by participants in the web-app will only be identified by their&#xD;
      unique identification number and information will be transferred to an excel spread sheet.&#xD;
&#xD;
      Clinical records including electronic and written records will be reviewed to investigate any&#xD;
      febrile episodes and infections for incidence and duration of fever/infection and duration of&#xD;
      hospital stay until afebrile for 48 hrs. Any data collected from clinical records will be&#xD;
      stored on an excel web sheet which will be kept on an NHS computer. Data on the excel&#xD;
      spreadsheet will be identified using their unique identification number. Data will be&#xD;
      collected and analysed on an NHS computer. The person collecting the data (the principal&#xD;
      investigator) is also a member of the health care team and has access to clinical records as&#xD;
      part of routine care.&#xD;
&#xD;
      Participants will be invited to participate in an optional interview exploring their&#xD;
      experiences in taking part in the study. This will take up to 45 minutes and can be done over&#xD;
      the phone or in person whilst in the hospital. The interviews will be recorded using an&#xD;
      encrypted digital audio recorder.&#xD;
&#xD;
      Participants who chose to decline will also be invited to a short optional interview&#xD;
      exploring why they chose to decline. This will approximately be a 10 minute discussion which&#xD;
      will take place when the participant/their parent disclose they have decided to decline and&#xD;
      will only take place if both the participant/parent and interviewer (the chief investigator)&#xD;
      is present in the hospital.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 20, 2019</start_date>
  <completion_date type="Anticipated">August 20, 2019</completion_date>
  <primary_completion_date type="Anticipated">July 20, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Double blinded randomised-controlled feasibility study</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The liquid probiotic/placebo will be blinded by the pharmacy team and LTHT</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Recruitment</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of eligible participants successfully recruited to the MaCROS study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recruitment</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion and number of eligible participants successfully recruited to the MaCROS study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Compliance of taking the probiotic/placebo</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of participants who are able to complete the 14 day course</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Compliance of filling in the paper/web-app diary</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of participants who are able to fill in and return the diary for 21 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cost-benefit evaluation of the study</measure>
    <time_frame>6 months</time_frame>
    <description>Cost-benefit analysis of undertaking the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of mucositis in both groups</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of participants who develop mucositis in both groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of mucositis in both groups</measure>
    <time_frame>6 months</time_frame>
    <description>Mean difference of mucositis (if possible) between both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants who develop fever</measure>
    <time_frame>6</time_frame>
    <description>Proportion of participants who develop fever Mean difference of fever (if possible) between both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate responsible guardian/participants experience of the MaCROS study</measure>
    <time_frame>6 months</time_frame>
    <description>This optional part of the study will be done by undertaking recorded telephone or face to face interview</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Pediatric Cancer</condition>
  <arm_group>
    <arm_group_label>Probiotic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will start the course of liquid probiotic on the first day of their course of chemotherapy. This can be taken orally, or using an nasogastric or gastrostomy tube and will continue this for 14 days. Doses will be adjusted according to the age of the participant as follows:&#xD;
1-4 years:20ml once a day 4-11 years: 0.5ml/kg once a day 12-18 years: 1ml/kg once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will start the course placebo on the first day of their course of chemotherapy. This can be taken orally or using an nasogastric or gastrostomy tube and will continue this for 14 days. Doses will be adjusted according to the age of the participant as follows:&#xD;
1-4 years:20ml once a day 4-11 years: 0.5ml/kg once a day 12-18 years: 1ml/kg once a day&#xD;
Placebo will be delivered in similar, packaging, appearance and taste.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic</intervention_name>
    <description>Liquid probiotic supplied by the company Symprove</description>
    <arm_group_label>Probiotic</arm_group_label>
    <other_name>Symprove liquid probiotic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo made of maltdextrin. Will be similar in taste and consistency</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients between the ages of 1 and 18 treated on paediatric cancer protocols receiving&#xD;
        chemotherapy on regimens likely to cause mucositis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who have already started the course of chemotherapy. Patients receiving&#xD;
        radiotherapy or surgery alone. Patients diagnosed with an immunodeficiency (excluding IgA).&#xD;
        Patients who have previously taken probiotics within the month prior to commencing the&#xD;
        course of chemotherapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hadeel Hassan, MBCHB MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Leeds</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hadeel Hassan, MBChB MSc</last_name>
    <phone>01133432596</phone>
    <phone_ext>01133432596</phone_ext>
    <email>umhh@leeds.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bob Phillips, MBChB PhD</last_name>
    <phone>01904321099</phone>
    <phone_ext>01133432596</phone_ext>
    <email>bob.phillips@york.ac.uk</email>
  </overall_contact_backup>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>December 21, 2018</last_update_submitted>
  <last_update_submitted_qc>December 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Leeds</investigator_affiliation>
    <investigator_full_name>Hadeel Hassan</investigator_full_name>
    <investigator_title>Clinical Research Fellow</investigator_title>
  </responsible_party>
  <keyword>pediatric</keyword>
  <keyword>cancer</keyword>
  <keyword>malignant haematology</keyword>
  <keyword>transplant</keyword>
  <keyword>probiotics</keyword>
  <keyword>mucositis</keyword>
  <keyword>infection</keyword>
  <keyword>supportive care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Mucositis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03785938
org study id: IRAS PROJECT ID: 246313
nct id: NCT03785938
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to evaluate the feasibility of an randomised-controlled trial to
      investigate the efficacy of liquid probiotics to prevent or reduce mucositis and infection in
      children diagnosed with cancer who are undergoing treatment with regimes likely to cause
      mucositis.
TRIAL DESIGN

      This will be a single-centre double-blind randomised-controlled feasibility study.

      TRIAL SETTING

      This study will take place at Leeds Teaching Hospital Trust (LTHT), Leeds UK. Participants
      will be approached whilst admitted as inpatients (typically the paediatric haematology
      oncology wards) and during outpatient clinics.

      METHOD

      Allocation sequence from a randomisation schedule will be generated A screening or trial ID
      number will be assigned to each participant.

      The allocation sequence will be concealed from health care professionals, participants and
      families. Only the pharmacy team involved in randomisation, allocation will not be blinded to
      allocation sequence and generation.

      Following identification, confirmation of eligibility, consent and allocation of trial ID of
      the participant, a prescription will be produced and the probiotic or placebo will be
      allocated accordingly.

      Appearance of the intervention and placebo will be similar in appearance, smell and taste.
      The placebo will include maltdextrin (a polysaccharide). Both the probiotic and placebo will
      be produced by the company Symprove.

      Participants will start the course of probiotic or placebo on the first day of their course
      of chemotherapy orally, or using an nasogastric or gastrostomy tube and will continue this
      for 14 days. Doses will be adjusted according to the age of the participant as follows:

      1-4 years:20ml once a day 4-11 years: 0.5ml/kg once a day 12-18 years: 1ml/kg once a day
      Placebo will be delivered in similar, packaging, appearance and taste.

      Participants or their parents will be asked to fill in a diary (paper or electronic using a
      web-app) daily for 21 days in total. The diary will include questions to assess nausea,
      vomiting, diarrhoea, pain and oral mucositis. An example of the patient diaries offered is
      supplied. Either the participant or parent will fill in the diary on a daily basis for a
      minimum of 21 days.

      The web-app is an electronic version of the paper diary. Participants will to chose their
      preferred method. Participants will be given the URL which they can download onto their phone
      as a web-app. Data provided by participants in the web-app will only be identified by their
      unique identification number and information will be transferred to an excel spread sheet.

      Clinical records including electronic and written records will be reviewed to investigate any
      febrile episodes and infections for incidence and duration of fever/infection and duration of
      hospital stay until afebrile for 48 hrs. Any data collected from clinical records will be
      stored on an excel web sheet which will be kept on an NHS computer. Data on the excel
      spreadsheet will be identified using their unique identification number. Data will be
      collected and analysed on an NHS computer. The person collecting the data (the principal
      investigator) is also a member of the health care team and has access to clinical records as
      part of routine care.

      Participants will be invited to participate in an optional interview exploring their
      experiences in taking part in the study. This will take up to 45 minutes and can be done over
      the phone or in person whilst in the hospital. The interviews will be recorded using an
      encrypted digital audio recorder.

      Participants who chose to decline will also be invited to a short optional interview
      exploring why they chose to decline. This will approximately be a 10 minute discussion which
      will take place when the participant/their parent disclose they have decided to decline and
      will only take place if both the participant/parent and interviewer (the chief investigator)
      is present in the hospital.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double blinded randomised-controlled feasibility study
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The liquid probiotic/placebo will be blinded by the pharmacy team and LTHT
measure: Recruitment
time frame: 6 months
description: Proportion of eligible participants successfully recruited to the MaCROS study
measure: Recruitment
time frame: 6 months
description: Proportion and number of eligible participants successfully recruited to the MaCROS study
measure: Compliance of taking the probiotic/placebo
time frame: 6 months
description: Proportion of participants who are able to complete the 14 day course
measure: Compliance of filling in the paper/web-app diary
time frame: 6 months
description: Proportion of participants who are able to fill in and return the diary for 21 days
measure: Cost-benefit evaluation of the study
time frame: 6 months
description: Cost-benefit analysis of undertaking the study
measure: Incidence of mucositis in both groups
time frame: 6 months
description: Proportion of participants who develop mucositis in both groups.
measure: Comparison of mucositis in both groups
time frame: 6 months
description: Mean difference of mucositis (if possible) between both groups
measure: Proportion of participants who develop fever
time frame: 6
description: Proportion of participants who develop fever Mean difference of fever (if possible) between both groups
measure: Evaluate responsible guardian/participants experience of the MaCROS study
time frame: 6 months
description: This optional part of the study will be done by undertaking recorded telephone or face to face interview
arm group label: Probiotic
arm group type: Experimental
description: Participants will start the course of liquid probiotic on the first day of their course of chemotherapy. This can be taken orally, or using an nasogastric or gastrostomy tube and will continue this for 14 days. Doses will be adjusted according to the age of the participant as follows:
1-4 years:20ml once a day 4-11 years: 0.5ml/kg once a day 12-18 years: 1ml/kg once a day
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will start the course placebo on the first day of their course of chemotherapy. This can be taken orally or using an nasogastric or gastrostomy tube and will continue this for 14 days. Doses will be adjusted according to the age of the participant as follows:
1-4 years:20ml once a day 4-11 years: 0.5ml/kg once a day 12-18 years: 1ml/kg once a day
Placebo will be delivered in similar, packaging, appearance and taste.
intervention type: Dietary Supplement
intervention name: Probiotic
description: Liquid probiotic supplied by the company Symprove
arm group label: Probiotic
other name: Symprove liquid probiotic
intervention type: Other
intervention name: Placebo
description: Placebo made of maltdextrin. Will be similar in taste and consistency
arm group label: Placebo
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: Hadeel Hassan, MBCHB MSc
role: Principal Investigator
affiliation: University of Leeds
last name: Hadeel Hassan, MBChB MSc
phone: 01133432596
phone ext: 01133432596
email: umhh@leeds.ac.uk
last name: Bob Phillips, MBChB PhD
phone: 01904321099
phone ext: 01133432596
email: bob.phillips@york.ac.uk
responsible party type: Principal Investigator
investigator affiliation: University of Leeds
investigator full name: Hadeel Hassan
investigator title: Clinical Research Fellow
mesh term: Infections
mesh term: Mucositis
sharing ipd: No