Clinical trial NCT06390176: Lactobacillus Rhamnosus GG Alleviates Oral Mucositis in Patients Undergoing Radiotherapy
Official title: Lactobacillus Rhamnosus LGG 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
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 132
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 rhamnosus GG (LGG) is a type of lactic acid bacterium, which is an important component of the microbiota in many parts of the human body.

Lactobacillus rhamnosus GG (LGG) is a lactic acid bacterium found in the human body, extensively researched for its probiotic properties. It has been tested in clinical trials for preventing and treating oral mucosal reactions during intensified radiotherapy for head and neck squamous cell carcinoma. LGG adheres well to epithelial layers, produces a protective biofilm, and modulates immune responses. It shows promise in reducing radiation-induced oral mucositis and can be safely used in infant formula. Additionally, a daily dosage of 3×10\^9 CFU of LGG has been effective in treating irritable bowel syndrome without adverse effects

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.

LGG has been used in clinical trials for the prevention and treatment of oral mucosal reactions during intensified radiotherapy for head and neck squamous cell carcinoma (including nasopharyngeal carcinoma). It was isolated from a healthy adult's fecal sample and possesses good growth characteristics and the ability to adhere to epithelial layers. It has long been one of the most extensively researched and applied probiotic strains, utilized in various commercially available probiotic products. Its beneficial effects have been extensively studied in clinical trials and human intervention studies, including its role in preventing and treating gastrointestinal infections and diarrhea, stimulating immune responses, and even preventing certain allergic symptoms.

In addition to producing a biofilm that mechanically protects the mucosa, reduces epithelial cell apoptosis, and maintains cell cytoskeleton integrity, LGG also exhibits immunomodulatory properties. It protects the epithelium from radiation damage by reducing TLR-2/COX-2 activation and regulates the protein levels of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-6, and monocyte chemotactic protein-1 in tissues, actively participating in host defense processes. It can also reduce the number of pathogenic bacteria and regulate colony distribution.

The occurrence and development of radiation-induced oral mucositis are closely related to cellular immunity. A series of pro-inflammatory cytokines produced by immune cells such as tumor necrosis factor-alpha and interleukin-6 will positively feedback to amplify the inflammatory response of radiation-induced oral mucositis.

Regarding safety, LGG can be added to infant formula as a probiotic. Furthermore, studies have shown that a dosage of 3×10\^9 CFU of LGG per day can be used to treat irritable bowel syndrome (IBS) without causing disease or toxicity in the body. Therefore, Lactobacillus rhamnosus GG holds promise as a potential approach for preventing and treating radiation-induced oral mucositis.

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
Secondary outcomes:
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
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: Functional assessment of cancer therapy-head and neck (FACT- H&N) quality of life questionnaire
timeFrame: 1 week before 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: