Clinical trial NCT06285591: Lactobacillus Reuteri Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors
Official title: Lactobacillus Reuteri Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Oral Mucositis (Ulcerative) Due to Radiation
Lead sponsor: West China Hospital
Sponsor class: OTHER
Collaborators: name: The General Hospital of Western Theater Command
First posted: 2024-02-29
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Primary outcomes:
measure: The incidence of Severe Oral mucositis (WHO grade ≥3)
timeFrame: From the start of radiotherapy to 8 weeks after completion of radiotherapy
measure: The time to onset of Severe Oral mucositis (WHO grade ≥3)
timeFrame: From the start of radiotherapy to 8 weeks after completion of radiotherapy
measure: The duration of Severe Oral mucositis (WHO grade ≥3)
timeFrame: From the start of radiotherapy to 8 weeks after completion of radiotherapy
Secondary outcomes:
measure: Taste function
timeFrame: 1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy (the last radiation dose received, usually 6 or 6.5 weeks); and 1, 3, 6, 9 and 12 months after the end of radiotherapy
measure: Xerostomia summated xerostomia inventory (SXI)
timeFrame: 1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy (the last radiation dose received, usually 6 or 6.5 weeks); and 1, 3, 6, 9 and 12 months after the end of radiotherapy
measure: European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30
timeFrame: 1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy (the last radiation dose received, usually 6 or 6.5 weeks); and 1, 3, 6, 9 and 12 months after the end of radiotherapy
measure: Adverse events
timeFrame: From the first day of radiotherapy to the day of the last radiation dose received, usually 6 or 6.5 weeks
measure: Oral activities scores
timeFrame: The time period is the period from the start of radiotherapy to the completion of radiotherapy. The evaluation period is approximately 6 weeks and 6 1/2 weeks
measure: Mouth and throat soreness (MTS) scores
timeFrame: The time period is the period from the start of radiotherapy to the completion of radiotherapy.The evaluation period is approximately 6 weeks and 6 1/2 weeks
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Xingchen Peng
role: PRINCIPAL_INVESTIGATOR
References: