A Phase 2 interventional study of Lactobacillus casei and Lactobacillus rhamnosus in Probiotics, Gastrointestinal Diseases and Precursor Cell Lymphoblastic Leukemia-Lymphoma, sponsored by National Institute of Pediatrics, Mexico. Enrolling by invitation at 1 site in Mexico. Open to participants aged 6 Years to 17 Years. Per ClinicalTrials.gov, last updated 2025-03-14.
Sponsored by National Institute of Pediatrics, Mexico · Phase 2, Interventional, and Prevention
Background: Acute lymphoblastic leukemia (ALL) is a common malignant neoplasm in children. Although chemotherapy achieves remission in over 70% of cases, it can cause gastrointestinal toxicity in up to 32.5%. Some studies suggest that administering probiotics reduces this risk, but the evidence remains inconsistent.
Objective: To evaluate the effectiveness and safety of administering L. casei, L. rhamnosus or B. bifidum compared to a placebo for the prevention of gastrointestinal toxicity, decreased intestinal permeability, and changes in intestinal microbiota in pediatric patients diagnosed with acute lymphoblastic leukemia receiving chemotherapy.
Methods: A total of 120 participants aged 6 to 17 years, diagnosed with ALL and receiving consolidation phase chemotherapy without gastrointestinal comorbidities, will be included. Participants will be administered daily 2 capsules containing either 1) L. casei, 2) L. rhamnosus, 3) B. bifidum or 4) placebo daily for 8 weeks. The clinical status of the participants will be evaluated weekly by the oncology service to determine the presence of gastrointestinal toxicity and adverse events. Changes in intestinal permeability will be assessed by measuring beta-lactoglobulin in a blood sample using the ELISA technique, while changes in the intestinal microbiota will be analyzed by genomic sequencing at baseline and at the end of follow-up.
Statistical analysis: Descriptive analysis will use measures of central tendency and dispersion. For quantitative variables, the mean and standard deviation or median with minimum and maximum values will be calculated depending on the distribution type. Frequencies and proportions will be calculated for qualitative variables, presented in tabular and graphical form. To compare the quantitative variables between the four interventions, a multi-way ANOVA test will be used.
The risk of gastrointestinal toxicity and adverse events will be analyzed by calculating the relative risk and 95% confidence interval. Differences between the interventions will be analyzed using survival analysis with the Kaplan-Meier and Log-Rank tests. Sequencing data will be analyzed using the Qiime2 program, filtered to generate a phylogenetic tree using the Silva database. Corresponding plots will be generated for each taxonomic level. Alpha (intra-group) and Beta (inter-group) diversity will be presented by ordination plots using principal component analysis with the ANCOM program
Background Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by the uncontrolled proliferation of immature lymphoid cells. It is the most common neoplasm in children, representing up to 53.1% of all oncologic processes in Mexico [1-6]. Fortunately, with the current chemotherapeutic treatments, disease remission is achieved in 98% of cases; however, the chemotherapeutic treatments have side effects that can lead to gastrointestinal toxicity (7.7 to 32.5%), which is associated with up to 50% mortality.
Among the most common gastrointestinal manifestations resulting from this toxicity are mucositis, pancreatitis (2 to 8%), diarrhea (10 to 82%), and colitis associated with decreased Bacillus spp and Bidifobacterium spp, increasing the risk of necrosis and intestinal perforation of the terminal ileum and cecum. Hence, several studies have been conducted to identify agents that can reduce the incidence of gastrointestinal toxicity like as probiotics which are a group of saprophytic microorganisms (bacteria, viruses, fungi and protozoa) that live in equilibrium on the skin and mucous membranes, mainly in the intestine, have garnered attention.
Probiotics are known to have several beneficial functions such as promoting the absorption of carbohydrates, short-chain fatty acids and calcium; facilitating the synthesis of lipids and vitamins; modulate and reduce the concentration of inflammatory mediators in the intestinal mucosa; improve mucosal blood flow, thus reducing the risk of ischemic areas in the intestine; and strengthen the immune system.
Although research has been conducted on the use of probiotics to prevent or reduce the toxic effects of chemotherapy, the results are still inconclusive because the effect of probiotics has been analyzed in multiple combinations, which makes it difficult to distinguish the specific effects per phylum. This complicates the generation of standardized therapeutic schemes to improve the quality of care of these patients. If this project successfully identifies the effectiveness and safety of these probiotics, it will enable to development of new therapeutic strategies aimed at improving the quality of healthcare for these patients, reducing the frequency and severity of gastrointestinal complications secondary to the administration of chemotherapy.
Objective To evaluate the effectiveness and safety of the administration of Lactobacillus casei, Lactobacillus rhamnosus and Bifidobacterium bifidum compared to placebo in reducing the risk of gastrointestinal toxicity, decreasing intestinal permeability, and changing intestinal microbiota without the development of adverse effects in pediatric patients diagnosed with ALL receiving consolidation chemotherapy in the Oncology Service of the Instituto Nacional de Pediatría.
General Description of the Study
Participant selection and consent:
Initial Assessments:
A) Physical examination:
B) Anthropometry
C) Nutritional Status
D) Body composition
E) Fecal samples
F) Serum samples
Assessments will be conducted weekly for clinical condition, anthropometry, and body composition at weeks 1, 4, and 8, and fecal and serum samples at weeks 1 and 8.
Preparation of interventions:
Participant Allocation:
Intervention Administration:
Clinical Evaluation:
Data Collection:
The sample size was calculated based on data from the study by Reyna-Figueroa, which reported a 0% incidence of diarrhea during the administration L. rhamnosus compared to 10% in participants who did not receive probiotics. Using the formula for proportions, with an alpha error of 0.05, 80% power, and estimating a loss rate of 20%, a sample size of 30 participants was determined for each of the four groups.
Statistical analysis A descriptive analysis will be performed using measures of central tendency to understand the characteristics of the studied sample and to determine the type of distribution of each variable using the Kolmogorov-Smirnoff normality test. For quantitative variables, the mean and standard deviation or median with minimum and maximum values will be calculated, depending on the type of distribution and summarized in tabular form; and data graphically represented by boxplot or bars chats as appropriate.
To compare the quantitative variables between the four interventions, a multi-way ANOVA test will be used. For qualitative variables, the chi-squared test will be used to compare the groups, adjusting for the nutritional status of the participants.
The risk of gastrointestinal toxicity and adverse events will be analyzed by the relative risk or Peto's odds ratio and 95% confidence interval. Differences between the interventions will be analyzed using survival analysis with the Kaplan-Meier and Log-Rank tests. Sequencing data will be analyzed using the Qiime2 program, filtered to generate a phylogenetic tree using the Silva database. Corresponding plots will be generated for each taxonomic level. Alpha (intra-group) and Beta (inter-group) diversity will be presented by ordination plots using principal component analysis with the ANCOM program.
Noted that patients who drop out of the study will have their results analyzed up to their last record, and all analyses will be conducted on an intention-to-treat basis.
548 studies on the registry are indexed under Gastrointestinal Diseases; 101 are open to participants now.
This study's planned enrollment of 120 is above the median of 80 across 388 interventional studies indexed under Gastrointestinal Diseases.
Browse Gastrointestinal Diseases studies →National Institute of Pediatrics, Mexico is the lead sponsor of 8 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral administration of 1 capsule with Lactobacillus casei (2.5 billion CFU + microcrystalline cellulose) before breakfast and another capsule before lunch, for a total dose of 5 billion CFU/day.
Biological: Lactobacillus casei
Oral administration of 1 capsule with Lactobacillus rhamnosus (2.5 billion CFU + microcrystalline cellulose) before breakfast and another capsule before lunch, for a total dose of 5 billion CFU/day.
Biological: Lactobacillus rhamnosus
Oral administration of 1 capsule with Bifidobacterium bifidum (1 billion CFU + microcrystalline cellulose) before breakfast and another capsule before lunch, for a total dose of 2 billion CFU/day.
Biological: Bifidobacterium bifidum
Oral administration of 1 capsule of 300 mg of microcrystalline cellulose before breakfast and another before lunch (600 mg/day).
Dietary Supplement: Placebo
Lacticaseibacillus casei is a species of Gram-positive anaerobic bacteria found in the intestine and mouth of humans. This lactic acid-producing bacterium is used in the dairy industry in the production of probiotic foods.
A live form of a bacterium that makes lactic acid (a substance derived from milk sugars and also made by the body). Lactobacillus rhamnosus GG is given to help with digestion and normal bowel function. In addition, it may help maintain a healthy gastrointestinal tract. It is being studied for the prevention of infections in patients who received donor stem cell transplants and for other conditions.
B. bifidum is an essential bacteria found in the human intestine. When it is low or absent all together in the human intestine, it is an indication of being in an unhealthy state. Intestinal flora can be improved if someone takes oral B. bifidum. Also, oral B. bifidum is used for other things such as therapy for enteric and hepatic disorders, for activating the immune response, and for preventing some cancers
Microcrystalline cellulose is a term for refined wood pulp and is used as a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production.The most common form is used in vitamin supplements or tablets
Prevention of Mucositis
Inflammation of the oral mucosa and gastrointestinal tract, triggered by the activation of inflammatory cytokines. For the evaluation, the pediatric oncologist will perform the physical examination of the oral cavity and report his findings as follows: * Number of participants with mucositis * Participants with mucositis will be evaluated with: A) The number and location of lesion(s). B) The maximum diameter of the largest lesion in centimeters. C) The severity of lesions Grade 1: Mucosal erythema, preserved feeding Grade 2: Focal pseudomembranous ulceration, modified food intake Grade 3: Confluent pseudomembranous ulcers, bleeding with minimal trauma, inability to feed or hydrate. Grade 4: Tissue necrosis, significant spontaneous bleeding
Time frame: 8 weeks
Prevention of Diarrhea
Increase in stool frequency or a decrease in stool consistency. For the evaluation, the pediatric oncologist will question the participant about the characteristics of the bowel movements and perform a physical examination of the abdomen. His findings will be reported as follows: The findings will be recorded as follows: * Number of participants with diarrhea * Participants with diarrhea will be evaluated with: A) Number of bowel movements per day B) Duration of diarrhea in days C) Stool content: None, blood, mocus, fat, food D) Classification of the diarrhea episode: Grade 1: Fewer than 4 stools per day. Grade 2: 4 to 6 stools per day, requiring intravenous hydration for less than 24 hours. Grade 3: More than 7 stools per day, requiring IV hydration for more than 24 hours, and necessitating hospitalization. Grade 4: Severe dehydration with hemodynamic consequences, requiring urgent IV hydration.
Time frame: 8 weeks
Prevention of Colitis
Inflammation and edema of the intestinal mucosa accompanied by abdominal pain, watery and bloody diarrhea. For the evaluation, the pediatric oncologist and pediatric surgeon, will perform a physical examination, laboratory and imaging studies. Findings will be recorded as follows: * Number of participants with colitis * Participants with colitis will be assessed with: A) Pain intensity using a visual analog scale (0 = no pain to 10 = severe pain). B) Location of pain (generalized or in one or more of the 9 abdominal regions) C) Duration of abdominal pain in days D) Classification of colitis: Grade 1 = asymptomatic Grade 2 = abdominal pain, presence of mucus or blood on evacuation Grade 3 = abdominal pain, fever, changes in evacuation rhythm with ileus or signs of peritoneal irritation. Grade 4 = Intestinal perforation, ischemia, hemorrhage, toxic megacolon or intestinal necrosis.
Time frame: 8 weeks
Adverse events (flatulence)
Production of intestinal gas mixture that is expelled through the rectum. For evaluation, the pediatric oncologist will ask the participant if there has been an increase in the frequency and amount of intestinal gas production during the week, and depending on the characteristics of the abdomen, flatulence will be classified according to the number of gases expelled per day. The findings will be recorded as follows: - Number of participants with gas. Absence \< 25 gases per day Presence \> 25 gases per day
Time frame: 8 weeks
Adverse events (distention)
Increased abdominal girth due to excessive gas in the bowel For evaluation, the pediatric oncologist will ask the participant if he/she has had an increase in abdominal girth during the week and will measure the abdominal girth using a circumference tape placed around the midpoint between the lower edge of the last rib and the upper edge of the iliac crest without applying pressure and will ask the participant to take a deep breath and at the moment of exhalation the measurement will be taken in centimeters.
Time frame: 8 weeks
Adverse events (constipation)
Infrequent bowel movements accompanied by scanty and hard stools. For evaluation, the pediatric oncologist and pediatric surgeon will ask the participant if has had difficulty passing stools during the week and will perform a physical examination. The findings will be recorded as follows: * Number of participants with constipation absent = \> 1 defecation per day present \< 1 defecation per day * Participants with constipation will be assessed with: A) Frequency of defecation per week B) Length of constipation in days C) Classification of constipation: Grade 1 = occasional or intermittent symptoms, sporadic use of laxatives, dietary changes, or need for enemas. Grade 2 = persistent symptoms with frequent use of laxatives or enemas Grade 3 = symptoms interfere with activities of daily living and require manual bowel movements Grade 4 = risk of death from bowel obstruction or toxic megacolon
Time frame: 8 weeks
Adverse events (vomiting)
Violent expulsion of gastric contents by mouth. To assess this, the pediatric oncologist will ask the participant if he/she has experienced this during the week. The findings will be recorded as follows: * Number of participants who vomited absent present \> 1 event per day * Participants with vomiting will be assessed with: A) Frequency of vomiting per day. B) Duration of vomiting C) Volume of vomiting D) Content of vomiting: * water * blood * mucus * food
Time frame: 8 weeks
Blood Beta-Lactoglobulin Concentration
To determine the functional status of the intestinal wall as a selective barrier to the passage of toxic substances and dietary proteins into the blood (intestinal permeability), the medical oncologist will take a peripheral blood sample by venipuncture and analyze it by sandwich enzyme immunoassay technique for the detection of antibodies against beta-lactoglobulin at the beginning and end of the participant's follow-up. The results will be reported in ng/mL.
Time frame: 8 weeks
Changes in alpha and beta diversity of the intestinal microbiota
Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals.The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota.The gut is the main location of the human microbiome.The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut-brain axis
Time frame: 8 weeks
Adverse events (fever)
Increase in body temperature \> 38° C in response to a medical condition. For evaluation, the pediatric oncologist will ask about the presence of fever during the week and will take the body temperature with a digital thermometer. The findings will be recorded as follows - Number of participants with fever absent \< 38 °C present \> 38 °C
Time frame: 8 weeks
Adverse events (nausea)
Feeling of unpleasantness or intense disgust with proximity to vomiting due to an triggering event. To assess this, the pediatric oncologist will ask the participant if he/she is experiencing, or has experienced during the week, a feeling of intense disgust. The findings are recorded as follows - Number of participants with nausea absent present
Time frame: 8 weeks
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Lacticaseibacillus casei · Lactobacillus rhamnosus · Bifidobacterium bifidum
National Institute of Pediatrics, Mexico