Lactobacillus Rhamnosus GG Alleviates Oral Mucositis in Patients Undergoing Radiotherapy

NCT ID: NCT06390176

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-10
• Study Completion Date: 2025-03-31

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.

Conditions

Oral Mucositis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Control group

Placebo-containing tablets

Group Type: PLACEBO_COMPARATOR

Placebo-containing tablets

Intervention Type: DIETARY_SUPPLEMENT

Starch preparations that look and taste like Lactobacillus rhamnosus GG powder

Radiotherapy

Intervention Type: RADIATION

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.

Experimental group

Lactobacillus rhamnosus GG (LGG)

Group Type: EXPERIMENTAL

Lactobacillus rhamnosus GG powder

Intervention Type: DIETARY_SUPPLEMENT

Lactobacillus rhamnosus GG powder (PROBIOTICS Powder, USA) contained no less than 5×10\^8 CFU viable cells of Lactobacillus rhamnosus GG as the active ingredient.

Radiotherapy

Intervention Type: RADIATION

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.

Interventions

Lactobacillus rhamnosus GG powder

Lactobacillus rhamnosus GG powder (PROBIOTICS Powder, USA) contained no less than 5×10\^8 CFU viable cells of Lactobacillus rhamnosus GG as the active ingredient.

Intervention Type: DIETARY_SUPPLEMENT

Placebo-containing tablets

Starch preparations that look and taste like Lactobacillus rhamnosus GG powder

Intervention Type: DIETARY_SUPPLEMENT

Radiotherapy

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.

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xingchen Peng

PhD, Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xingchen Peng

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xingchen Peng

Role: CONTACT

pxx2014@163.com

+86 18980606753

Facility Contacts

Xingchen Peng, PhD

Role: primary

pxx2014@163.com

+86 18980606753

Other Identifiers

2023-1747

Identifier Type: -

Identifier Source: org_study_id