Effectiveness of Probiotics for the Prevention of Gastrointestinal Toxicity in Children with Leukemia

Summary

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

Conditions

• Probiotics
• Gastrointestinal Diseases
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

BIOLOGICAL

Lactobacillus casei

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.

BIOLOGICAL

Lactobacillus rhamnosus

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.

BIOLOGICAL

Bifidobacterium bifidum

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

DIETARY_SUPPLEMENT

Placebo

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

Sponsors & Collaborators

• National Institute of Pediatrics, Mexico

  lead OTHER_GOV

Principal Investigators

• Sara Espinosa-Padilla, Ph.D. · National Institute of Pediatrics

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

6 Years

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-01

Primary Completion

2025-12-31

Completion

2026-08-31

FDA Drug

Yes

Countries

• Mexico

Study Locations