Mucositis and Infection Reduction With Liquid Probiotics in Children With Cancer (MaCROS)

Mucositis and Infection Reduction With Liquid Probiotics in Children With Cancer: a Randomised-controlled Feasibility Study

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.

Study Overview

• Status: Unknown
• Conditions: Pediatric Cancer
• Intervention / Treatment: Dietary supplement: Probiotic; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hadeel Hassan, MBChB MSc; Phone Number: 01133432596 01133432596; Email: umhh@leeds.ac.uk
• Study Contact Backup: Name: Bob Phillips, MBChB PhD; Phone Number: 01133432596 01904321099; Email: bob.phillips@york.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients between the ages of 1 and 18 treated on paediatric cancer protocols receiving chemotherapy on regimens likely to cause mucositis.

Exclusion Criteria:

Patients who have already started the course of chemotherapy. Patients receiving radiotherapy or surgery alone. Patients diagnosed with an immunodeficiency (excluding IgA). Patients who have previously taken probiotics within the month prior to commencing the course of chemotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; 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	Dietary supplement: Probiotic; Liquid probiotic supplied by the company Symprove; Other Names: Symprove liquid probiotic
Placebo Comparator: Placebo; 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.	Other: Placebo; Placebo made of maltdextrin. Will be similar in taste and consistency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment	Proportion of eligible participants successfully recruited to the MaCROS study	6 months
Recruitment	Proportion and number of eligible participants successfully recruited to the MaCROS study	6 months
Compliance of taking the probiotic/placebo	Proportion of participants who are able to complete the 14 day course	6 months
Compliance of filling in the paper/web-app diary	Proportion of participants who are able to fill in and return the diary for 21 days	6 months
Cost-benefit evaluation of the study	Cost-benefit analysis of undertaking the study	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of mucositis in both groups	Proportion of participants who develop mucositis in both groups.	6 months
Comparison of mucositis in both groups	Mean difference of mucositis (if possible) between both groups	6 months
Proportion of participants who develop fever	Proportion of participants who develop fever Mean difference of fever (if possible) between both groups	6
Evaluate responsible guardian/participants experience of the MaCROS study	This optional part of the study will be done by undertaking recorded telephone or face to face interview	6 months

Collaborators and Investigators

• Sponsor: University of Leeds
• Investigators: Principal Investigator: Hadeel Hassan, MBCHB MSc, University of Leeds

Publications and helpful links

General Publications

• Hassan H, Kinsey S, Phillips B. Mucositis reduction with probiotics in children with cancer: a randomised-controlled feasibility study. Arch Dis Child. 2022 Mar;107(3):259-264. doi: 10.1136/archdischild-2020-319968. Epub 2021 Jun 30.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 20, 2019
• Primary Completion (Anticipated): July 20, 2019
• Study Completion (Anticipated): August 20, 2019

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: transplant; cancer; pediatric; probiotics; infection; supportive care; mucositis; malignant haematology
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Infections; Mucositis
• Other Study ID Numbers: IRAS PROJECT ID: 246313

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No