The Efficacy and Safety of a Compound Glutamine Capsule in the Prevention of Chemotherapy-induced Mucositis

Study Overview
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Brief Summary
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Chemotherapy regimens not only improve the survival of patients with gastric cancer and colorectal cancer, but also cause obvious adverse reactions of digestive tract, such as chemotherapy-induced oral mucositis, abdominal pain, diarrhea, constipation and so on. These adverse reactions seriously affect the patients' quality of life and the efficacy of chemotherapy. Glutamine is a conditionally essential amino acid in the human body. Previous studies have shown that oral glutamine can help to keep the integrity of mucosal epithelium during chemotherapy and reduce the gastrointestinal side effects caused by chemotherapy. The addition of glutamine to parenteral nutrition can better maintain nitrogen balance and reduce the incidence of infection-related complications. A compound glutamine capsule, composed of L-glutamine and the traditional Chinese herbal formula Si-Jun-Zi-Tang which composed of ginseng, Atractylodes macrocephala, Poria cocos and licorice, has been widely used in China for 23 years to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy, ulcerative colitis, irritable bowel syndrome. However, so far, only a small sample of clinical trials have explored the role of glutamine in chemical mucositis, and there is a lack of prospective randomized controlled clinical trials to further verify its value in the prevention and treatment of chemical mucositis. The purpose of this study is to observe the efficacy and safety between a compound glutamine capsule and placebo in the prevention of chemotherapy-induced mucositis in patients with gastric cancer and colorectal cancer in a prospective, randomized, double-blind clinical trial.

Official Title
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The Efficacy and Safety of a Compound Glutamine Capsule in the Prevention of Chemotherapy-induced Mucositis in Patients With Gastrointestinal Tumors: a Prospective, Randomized, Controlled, Double-blind, Phase III Clinical Study

Conditions
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Mucositis, Chemotherapeutic Toxicity

Intervention / Treatment
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* Drug: a compound glutamine capsule
* Drug: a compound glutamine capsule simulated placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 years old; Sex: Male or female; Pathologically confirmed gastric adenocarcinoma or colorectal adenocarcinoma; Patients who had received standard chemotherapy containing platinum or irinotecan developed grade 1-3 (NCI-CTCAE, version4.0) diarrhea in the previous cycle and recovered to grade 0 after symptomatic treatment; Patients are planned to receive the same chemotherapy regimen and dose as the previous cycle; A baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; Adequate haematopoietic function of bone marrow: neutrophils≥1.5x109 / L, platelets≥75x109 / L; normal liver and kidney function: TBIL≤ 1 upper limit of normal (ULN); ALT and AST ≤2.5 ULN; creatinine≤1.5 ULN; Estimated life expectancy ≥ 3 months; Be willing and able to provide written informed consent for the trial. Exclusion Criteria: (Patient-Generated Subjective Global Assessment, PG-SGA)>9 or severe malnutrition (weight loss > 10% or serum albumin < 30 g/L or body mass index < 18.5 kg/m2); Patients with severe heart, lung and brain diseases; chronic hepatitis infection, liver cirrhosis, chronic nephritis, kidney dysfunction, etc; Patients with infection-related fever; Patients who are known to be allergic or intolerant to any of the ingredients used in the study; Patients with long-term chronic diarrhea, abdominal pain, constipation or other digestive tract diseases; patients with gastrointestinal symptoms before chemotherapy (≥grade 2 NCI-CTCAE, version 4.0); Synchronously receive other treatments that may cause diarrhea, such as radiotherapy; Patients who take drugs for microecological regulation of digestive tract such as Combined Bifidobacterium, ChangTai oral liquid, etc; Patients take traditional Chinese medicine or antibiotics; Unable to understand and sign the informed consent form; participants in other clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group C<br>during the current cycle of chemotherapy (need to be the same regimens as the previous cycle of chemotherapy, the same dose), patients take a compound glutamine capsules, from the first day of chemotherapy, orally 3 times a day after meals, 3 tablets each time, the course of treatment is 3 weeks. | Drug: a compound glutamine capsule<br>* A compound glutamine capsule was taken orally from the first day of chemotherapy, orally 3 times a day after meals, 3 tablets each time, the course of treatment is 3 weeks.<br>|
| Placebo Comparator: Group D<br>during the current cycle of chemotherapy (need to be the same regimens as the previous cycle of chemotherapy, the same dose), patients take a compound glutamine capsule simulated placebo, from the first day of chemotherapy, orally 3 times a day after meals, 3 tablets each time, the course of treatment is 3 weeks. | Drug: a compound glutamine capsule simulated placebo<br>* a compound glutamine capsule simulated placebo was taken orally from the first day of chemotherapy, orally 3 times a day after meals, 3 tablets each time, the course of treatment is 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall incidence of chemotherapy-induced diarrhea ≥ grade 1 | Overall incidence of chemotherapy-induced diarrhea ≥ grade 1 (according to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0) | At the end of Cycle 1(each cycle is 14/21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall incidence of gastrointestinal adverse events except diarrhea ≥ grade 1 | Overall incidence of gastrointestinal adverse events except diarrhea ≥ grade 1 (including oral mucositis, nausea, vomiting, abdominal pain, stomachache, and other types, according to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0) | At the end of Cycle 1(each cycle is 14/21 days) | 
| Overall incidence of grade 3/4 gastrointestinal adverse events | Overall incidence of grade 3/4 gastrointestinal adverse events according to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 | At the end of Cycle 1(each cycle is 14/21 days) |