Trial Title:
Lactobacillus Reuteri Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors
NCT ID:
NCT06285591
Condition:
Oral Mucositis (Ulcerative) Due to Radiation
Conditions: Official terms:
Head and Neck Neoplasms
Mucositis
Stomatitis
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Lactobacillus Reuteri Tablets
Description:
Lactobacillus Reuteri lozenges (NOW Foods, Sweden) contained no less than 2×10^8 CFU
viable cells of Lactobacillus Reuteri as the active ingredient.
Arm group label:
Experimental group
Intervention type:
Dietary Supplement
Intervention name:
Placebo-containing tablets
Description:
Starch preparations that look and taste like Lactobacillus Reuteri
Arm group label:
Control group
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
One of the inclusion criteria for the study was that patients with squamous carcinoma of
the head and neck (including nasopharyngeal carcinoma) needed to receive either
radiotherapy alone or simultaneous radiotherapy and chemotherapy, with radiotherapy using
intensity-modulated radiotherapy techniques.
Arm group label:
Control group
Arm group label:
Experimental group
Summary:
Radiation therapy is a common treatment modality in the management of head and neck
malignancies. However, head and neck tumors often have some adverse reactions when
receiving radiation therapy, such as dry mouth, change of taste, oral mucositis, etc.
Among them, the incidence of oral mucositis is more than 90%, and the incidence of oral
mucositis of degree 3 or more than degree 3 is more than 50%. Severe oral mucositis
seriously affects the quality of survival of patients. Lactobacillus Reuteri is a natural
flora of the human body that can be found in the gastrointestinal tract, skin, etc. Among
them, Lactobacillus Reuteri DSM 17938 and ATCC PTA 5289 can be isolated from healthy
mammals as well as poultry, and are common Lactobacillus strains marketed for the
production of oral probiotics, which are commonly used in infant formulas, among others.
In oral inflammatory diseases, it has been reported in the literature that Lactobacillus
Reuteri DSM 17938 and ATCC PTA 5289 can reduce gingival and periodontal inflammation,
mainly through the mechanisms of modulating the host inflammatory response and displacing
pathogenic bacteria. In terms of safety, oral Lactobacillus Reuteri has good stability,
very low pathogenic potential, and is not toxic to humans. Therefore, this study is a
placebo-controlled, multi-center, open, randomized controlled clinical study to evaluate
the efficacy of Lactobacillus Reuteri for the prevention of radioactive oral mucosal
reactions in intensity-modulated radiotherapy for head and neck tumors, including
nasopharyngeal carcinoma.
Detailed description:
Radiotherapy (RT) is an important treatment for head and neck malignant tumors and can be
used alone or in combination with chemotherapy as radical or adjuvant therapy. Despite
improvements in RT equipment and techniques, there are still a variety of acute oral
complications, including oral mucositis (OM), xerostomia, taste dysfunction, and oral
infection. OM is one of the most common acute radiation-related toxicity in head and neck
malignant tumor patients receiving RT, and approximately 50~70% of patients experience
severe oral mucositis (SOM). The painful inflammation and ulceration associated with OM
not only profoundly affect patients' ability to eat, swallow, and speak but also decrease
patients' tolerance to anti-cancer treatment, seriously impairing patients' quality of
life (QoL) and causing interruptions and cancellations of cancer treatment. Standard
treatment for OM focuses on pain control, rehydration, and good oral hygiene. For
patients with hematopoietic stem cell transplantation, palifermin (keratinocyte growth
factor-1) is recommended. Although some clinical strategies for OM such as non-steroidal
anti-inflammatory drugs, mucosal protective agents, growth factors and cytokines,
antibacterial, and pain relief drugs have been recommended by the Multinational
Association of Supportive Care in Cancer and International Society of Oral Oncology
(MASCC/ISOO), the therapeutic benefit is limited6. Thus, it is crucial to develop
effective drugs or treatment strategies to decrease radiation-induced mucosal toxicity.
The resident microbiota plays an important role in the pathogenesis and development of
radiation-induced OM. Microbiota can release pathogen-associated molecular patterns
(PAMPs) that bind to pathogen recognition receptors (PRR) and activate the initial innate
immune response, a known pathogenic pathway. Recent studies have suggested that dysbiosis
of oral microbial contributes to the occurrence and severity of radiation-induced OM and
manipulation of the patient microbial community may be key to preventing and treating
effectively OM. Probiotics are defined as live microorganisms which when administered in
adequate amounts can improve the microecological balance and confer a health benefit on
the host. Conventional probiotics typically belong to the genera Lactobacillus or
Bifidobacterium and Lactobacillus brevis CD2 is the most widely studied probiotic for
preventing cancer therapy-induced OM, but its effectiveness is still debated.
Lactobacillus Reuteri is the body's natural flora and can be found in the
gastrointestinal tract, skin, breast milk, etc. And they do not trigger infections in
healthy individuals15. Among them, Lactobacillus Reuteri DSM 17938 and ATCC PTA 5289 can
be isolated from healthy mammals as well as poultry, and are common Lactobacillus strains
used in the market for making oral probiotics16. Lactobacillus Reuteri DSM 17938 has been
reported to alleviate chronic inflammatory conditions such as infantile colic and
irritable bowel-syndrome17.In oral inflammatory diseases, Lactobacillus Reuteri DSM 17938
and ATCC PTA 5289 have been found to reduce gingival and periodontal inflammation, which
is mainly achieved through mechanisms such as modulation of the host inflammatory
response and displacement of pathogenic bacteria. The development of oral mucositis
caused by radiotherapy or chemoradiotherapy is associated with DNA damage and high
production of various inflammatory factors such as interleukin-1(IL-1), interleukin-6
(IL-6) and tumor necrosis factor-a(TNF-a). Recently, the results of the study by Nitasha
et al. showed that Lactobacillus Reuteri DSM 17938 and ATCC PTA 5289 can reduce oxidative
stress and Inflammation in a preclinical rodent model. All of the above imply
Lactobacillus reuteri's potential use in the prevention of OM.
The purpose of this placebo-controlled randomized trial was to investigate the prevention
effects of Lactobacillus Reuteri versus placebo in patients with head and neck malignant
tumors receiving RT.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients pathologically diagnosed with non-metastatic head and neck malignant
tumors;
2. Aged 18-80 years;
3. Eastern Cooperative Oncology Group performance status of ≤2;
4. Planning to receive definitive RT or postoperative adjuvant RT;
5. Normal liver, kidney and bone marrow function;
6. Sign informed consent.
Exclusion Criteria:
1. Known hypersensitivity or more severe allergies to Lactobacillus Reuteri components;
2. Those with poor compliance;
3. Pregnancy or breastfeeding;
4. History of head and neck radiotherapy;
5. Taking antifungal or viral medications one week prior to the start of radiation
therapy.
6. Other patients (with any other serious other medical condition) who, in the opinion
of the investigator, are not suitable for participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Xingchen Peng, PhD
Phone:
+86 18980606753
Email:
pxx2014@163.com
Start date:
November 10, 2023
Completion date:
December 10, 2024
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Collaborator:
Agency:
The General Hospital of Western Theater Command
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06285591
