Effects of Probiotics in Preventing Oral Mucositis

Effects of Probiotics Intake on Oral Microbiome and Mucosa Inflammation in Patients With Cytotoxic Therapy Induced Oral Mucositis: A Pilot Study

The study will be a randomized double blind prospective placebo controlled clinical study and aims to determine the therapeutic efficacy of Probiotics in Oral Mucositis pathogenesis in patients undergoing head and neck radiotherapy.

Study Overview

• Status: Unknown
• Conditions: Head-and-neck Cancer
• Intervention / Treatment: Drug: Lactobacillus Reuteri Oral Solution [BioGaia]; Drug: Placebos

Detailed Description

The study will be a randomized double blind prospective placebo controlled clinical study (Clinical Trial phase II) of 50 patients (25 in LR group, 25 in placebo group) with a confirmed cancer diagnosis requiring head and neck radiotherapy with a minimum dose of 6000cGy.

Patients will be randomly assigned to either of the treatment arms in a 1:1 ratio. The active agent; Lactobacillus reuteri Prodentis (Biogaia ®) will be supplied in droplet form by Pharma forte Singapore Pte Ltd and dosage used will be as recommended by manufacturer (5 drops/time twice a day which is equivalent to 4 X 108 CFU of live bacteria). The control agent will be identical in physical appearance and color to the study agent and will be made by the manufacturer.

Patients assigned to either LR group or placebo group will start from the first day of radiotherapy and continued until 2-week post radiation (approximately 8-9 weeks). Patients will be instructed to use the LR droplets twice a day according to manufacturer's instructions; once in the morning after breakfast and the other just before bedtime and to avoid any food/drinks 30 minutes before and after usage. Compliance with treatment will be elicited and recorded.

The dose selection is based on manufacturer's recommendations and is safe for use during pregnancy and breastfeeding. However, this is not an issue in this population as none of the patients should be pregnant or breastfeeding while receiving radiation and anti-neoplastic chemotherapy.

The PI will serve as the auditor for data quality assurance on a quarterly basis.Data collected on paper will be stored in the principal investigator's locked cabinet. Data will be entered into Microsoft Excel™ (2007) and double entered for accuracy. Data will be kept in a password secured portable computer and backed up to dedicated local back-up drive every week. Only group statistics will be reported. The database will only be accessible to investigators involved in and approved for the study. All data will be kept for 6 years after study completion to access data for publication of the work done, after which data will be destroyed.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital, Singapore
    • Contact: Catherine Hong, BDS; Phone Number: 1787 67795555; Email: denchhl@nus.edu.sg
    • Principal Investigator: Catherine Hong, BDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients who are 21 years of age or older
2. histological diagnosis of head and neck carcinoma available
3. undergoing head and neck radiotherapy of at least 6000cGY
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
5. no known allergy to Biogaia
6. able to give written informed consent, or have written consent given on their behalf.

Exclusion Criteria:

1. patients who cannot use the products or have it administered to them
2. patients with existing conditions predisposing to oral ulcer formation
3. patients with mucositis at baseline (prior to initiation of treatment)
4. previous radiotherapy to the head and neck region
5. female patients who are pregnant or breastfeeding
6. patients who have central venous catheters
7. patients who have impaired intestinal epithelial barrier
8. patients who have cardiac valvular disease
9. unable to give written informed consent, or are unable to have written consent given on their behalf.
10. inability to converse in English or Mandarin
11. severe immunosuppression (Absolute Neutrophil Count of less than 1500 cells/µL)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LR group; Lactobacillus Reuteri Oral Solution [BioGaia]	Drug: Lactobacillus Reuteri Oral Solution [BioGaia]; BioGaia Lactobacillus Reuteri drops; Other Names: Biogaia Prodentis
Placebo Comparator: Placebo group; Placebos: The control agent will not contain the active agent	Drug: Placebos; Placebo will be identical in physical appearance and color to the study agent and will be made by the manufacturer; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Mucositis (OM) Severity Assessment	To assess the severity of OM using Oral Mucositis Assessment Scale (OMAS)	Weekly review from baseline (Day 1 of Radiation) to 14 days after last radiation treatment
Oral Mucositis (OM) Severity Assessment	To assess the severity of OM (Grade 0-4) using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0	Weekly review from baseline (Day 1 of Radiation) to 14 days after last radiation treatment
Duration of Oral Mucositis (OM)	To assess the number of days of OM experienced i.e. start of OM still resolution of OMM	Weekly review from baseline (Day 1 of Radiation) to 14 days after last radiation treatment
Pain Severity of OM	Visual Analogue Scale (0-10)	Weekly review from baseline (Day 1 of Radiation) to 14 days after last radiation treatment
Quality of Life post Radiation	Composite score using the Oral Mucositis Daily Questionnaire (8 Item questionnaire)	Daily Patient Completed Questionnaire from baseline (Day 1 of Radiation) to 14 days after last radiation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Bacteria Analysis and Gene Expression Analysis	Oral samples will be collected at 2 time points: baseline (before start of head and neck radiotherapy) and at week 4 (Visit 5, midpoint) of radiotherapy.	Change between baseline and Week 4

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Catherine Hong, National University Hospital, Singapore

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: April 15, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: probiotics; oral mucositis; anti-neoplastic chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Stomatitis
• Other Study ID Numbers: 2017/00508

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