Effect of Synbiotic Supplementation on the Prevention of Mucositis in Cancer Patients Undergoing Chemotherapy

Effect of Synbiotic Supplementation on the Prevention of Mucositis in Cancer Patients Undergoing Chemotherapy: Randomized, Double-masked, Parallel, Single-center Clinical Trial

Introduction: In the 2023-2025 period, colorectal cancer (CRC) will be the third most common type of cancer in Brazil. The most commonly used therapeutic approaches are chemotherapy (QTx) and radiotherapy (RTx). QTx agents, such as capecitabine, affect both malignant cells and normal cells such as gastrointestinal, capillary and immune cells. Cellular damage in the gastrointestinal tract (GIT) results in various symptoms, such as mucositis and diarrhea. Diarrhea is linked to mucosal damage and can result in dehydration, malnutrition and hospitalization, leading to cardiovascular complications and death. Mucositis is inflammation that affects the GIT. This condition makes treatment difficult, leading to reductions, delays or interruption of QTx. These scenarios harm the patient's prognosis and quality of life, resulting in high costs for symptom control, nutritional assistance, management of secondary infections and hospitalization. The Mucositis Study Group (MASCC/ISOO) guidelines recommend the use of probiotics as a preventive measure against diarrhea in cancer patients undergoing QTx and/or RTx. However, the safety of using probiotics in immunosuppressed patients is still controversial and hypotheses are based on epidemiological and experimental studies. This makes it necessary to evaluate whether supplementation with pro- or synbiotics before chemotherapy would have the same beneficial results. Objective: To evaluate the effect of synbiotic supplementation on the prevention, incidence and severity of mucositis in cancer patients undergoing QTx. Method: This is a single-center parallel double-masked randomized clinical trial to be carried out at the Borges da Costa/UFMG Outpatient Clinic at Hospital das Clínicas in Belo Horizonte - Minas Gerais (HC-BH/MG). The inclusion criteria are patients diagnosed with CRC eligible for first-line treatment with Capecitabine, aged ≥ 18 years, both sexes, signed the informed consent form. The study was approved by CEP-UFMG. Expected results: It is expected that supplementation with synbiotics in the pre-QTx period will promote modulation of the microbiota and strengthening of the intestinal barrier, resulting in a lower incidence and severity of mucositis and diarrhea, improving the quality of life of these patients.

Study Overview

• Status: Recruiting
• Conditions: Colo-rectal Cancer
• Intervention / Treatment: Dietary supplement: Maltodextrin; Dietary supplement: Symbiotic

Detailed Description

Introduction: In the triennium 2023-2025, colorectal cancer (CRC) will be the third most common type of cancer in Brazil. The most used therapeutic approaches are chemotherapy (QTx) and radiotherapy (RTx). Chemotherapeutic agents, such as capecitabine, affect both malignant cells and normal cells such as gastrointestinal, capillary, and immune cells. Cellular damage in the gastrointestinal tract (GIT) results in various symptoms, such as mucositis and diarrhea. Diarrhea is linked to mucosal injury and can lead to dehydration, malnutrition, hospitalization, cardiovascular complications, and death. Mucositis, on the other hand, is inflammation that affects the GIT. This condition hinders treatment, leading to reductions, delays, or interruption of QTx. These scenarios impair the prognosis and quality of life of the patient, resulting in high costs for symptom control, nutritional support, management of secondary infections, and hospitalization. The Mucositis Study Group guidelines (MASCC/ISOO) recommend the use of probiotics as a preventive measure against diarrhea in cancer patients undergoing QTx and/or RTx. However, the safety of probiotic use in immunosuppressed patients is still controversial, and hypotheses are based on epidemiological and experimental studies. Therefore, it is necessary to evaluate whether supplementation with probiotics or symbiotics before chemotherapy would have the same beneficial results. Objective: The general objective of this study is to evaluate if symbiotic supplementation can reduce the incidence and severity of oral mucositis in cancer patients undergoing chemotherapy. Specific objectives include assessing the tolerability of supplementation, analyzing clinical and laboratory parameters related to mucositis, and investigating the impact of the intervention on the quality of life of patients. Methodology: This is a randomized, double-blind, parallel, single-center clinical trial to be conducted at the Borges da Costa Outpatient Clinic located at the Hospital das Clínicas of the Federal University of Minas Gerais in Belo Horizonte (HC-UFMG). Inclusion criteria involve adult patients, aged ≥ 18 years, of both sexes, diagnosed with colorectal cancer and candidates for first-line chemotherapy treatment with Capecitabine alone or in combination with Oxaliplatin, treated at HC/UFMG under the signature of the Informed Consent Form (ICF) and able to follow the research guidelines. The study was approved by the Research Ethics Committee of UFMG (CEP-UFMG) under protocol number CAAE 30177920.2.0000.5149. The study involves 80 participants distributed according to the chemotherapy protocol. Patients will be randomly divided into two groups designated as A and B: one control group receiving Maltodextrin, and the other intervention group receiving Symbiotic. The supplementation will be administered for 10 days, twice a day, before the start of chemotherapy treatment. Biological samples, such as feces and blood, will be collected for analysis of intestinal microbiota, short-chain fatty acid (SCFA) levels, presence of infection, intestinal permeability, and inflammatory markers. Biological collections will be performed at different time points throughout the study, including before supplementation (D0-D1), on the 10th day of supplementation (D10 pre-QTx), and on days 14 and 21 of the first chemotherapy cycle (D14-QTx and D21-QTx). Data will be collected through nutritional, anthropometric, and dietary assessments, including the Subjective Global Assessment (SGA), Anthropometric Assessment, Dietary Assessment (24h Recall and Food Frequency Questionnaire), as well as assessment of intestinal function and digestive complaints. Patients will be monitored daily, along with follow-up during treatment and data recording in the electronic medical record. Statistical analysis of the data will include sample size calculation, appropriate statistical tests, and an exploratory approach to evaluate clinical outcomes and study results. Expected Results It is expected that the results of this study will provide evidence on the efficacy of symbiotic supplementation in preventing oral mucositis in CRC patients undergoing chemotherapy. If the intervention proves to be effective, it could contribute to the development of more effective nutritional strategies in managing the side effects of oncological treatment, improving the quality of life and well-being of patients.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simone de Vasconcelos Generoso; Phone Number: +55(031) 988128650; Email: simonenutufmg@gmail.com

Study Locations

• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Recruiting
      • Escola de Enfermagem - UFMG
      • Contact: Simone V Generoso; Phone Number: +55(31) 988128650; Email: simonenutufmg@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Colorectal tumor in the first oncological treatment
• Age over 18 years old
• Both sexes
• Eligible for protocol with capecitabine alone or associated with oxaliplatin
• Patients WITHOUT colostomy or WITH colostomy in the transverse/descending/sigmoid region
• Patient undergoing Radiotherapy treatment associated with Chemotherapy
• Patients residing in Belo Horizonte and the metropolitan region
• Patients who Accept and sign the Informed Consent Form (TCLE)

Exclusion Criteria:

• Diagnosis of gastrointestinal carcinoid and stromal tumor (GIST)
• Patients with Ileostomy
• Patients with colostomy in the ascending region of the colon
• Inflammatory bowel diseases: Crohn's and Colitis
• Use of antibiotics and antifungals in the last 15 days
• Use of prebiotic/probiotic and/or synbiotic in the last 15 days
• Use of antidiarrheal medication in the last 15 days
• Presence of fever and mucus discharge
• Pregnant or breastfeeding women
• Patients who refuse to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Capecitabine alone control; n the Control Group, patients received Maltodextrin as supplementation	Dietary supplement: Maltodextrin; Maltodextrin, used as control, will be purchased from the company PRODIET® under the trade name Carboch®. Supplementation will be administered orally, twice a day, before lunch and dinner, for ten days before chemotherapy treatment. Patients will be guided by researchers on dilution (100 mL of filtered water) and the correct purchase of the modules. Consumption control will be carried out daily, via telephone contact.
Experimental: Capecitabine alone synbiotic; In the Intervention Group, patients received the symbiotic Simbioflora as supplementation.	Dietary supplement: Symbiotic; The synbiotic used will be Simbioflora® (commercial preparation containing 5.5g of FOS added with four species of probiotic, Lactobacillus paracasei LPC-31; Lactobacillus rhamnosus HN001; Lactobacillus acidophilus NCFM; Bifidobacterium lactis HN019, at a concentration of 109 UFC per strain) supplied by Farmoquímica S.A. Supplementation will be administered orally, twice a day, before lunch and dinner, for ten days before chemotherapy treatment. Patients will be guided by researchers on dilution (100 mL of filtered water) and the correct purchase of the modules. Consumption control will be carried out daily, via telephone contact.; Other Names: Simbioflora
Placebo Comparator: Capecitabine associated with control Oxaliplatin; n the Control Group, patients received Maltodextrin as supplementation	Dietary supplement: Maltodextrin; Maltodextrin, used as control, will be purchased from the company PRODIET® under the trade name Carboch®. Supplementation will be administered orally, twice a day, before lunch and dinner, for ten days before chemotherapy treatment. Patients will be guided by researchers on dilution (100 mL of filtered water) and the correct purchase of the modules. Consumption control will be carried out daily, via telephone contact.
Experimental: Capecitabine associated with synbiotic Oxaliplatin; In the Intervention Group, patients received the symbiotic Simbioflora as supplementation.	Dietary supplement: Symbiotic; The synbiotic used will be Simbioflora® (commercial preparation containing 5.5g of FOS added with four species of probiotic, Lactobacillus paracasei LPC-31; Lactobacillus rhamnosus HN001; Lactobacillus acidophilus NCFM; Bifidobacterium lactis HN019, at a concentration of 109 UFC per strain) supplied by Farmoquímica S.A. Supplementation will be administered orally, twice a day, before lunch and dinner, for ten days before chemotherapy treatment. Patients will be guided by researchers on dilution (100 mL of filtered water) and the correct purchase of the modules. Consumption control will be carried out daily, via telephone contact.; Other Names: Simbioflora

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal Microbiota	Fecal calprotectin measured by ELISA.	six months after collecting data from all research participants
Intestinal Microbiota	production of short-chain fatty acids.	six months after collecting data from all research participants
Intestinal Microbiota	analysis of intestinal microbiota composition by sequencing the 16S rRNA gene.	six months after collecting data from all research participants
Clinical Nutritional Diagnostic	Body mass index BMI in kg/m²	six months after collecting data from all research participants
Nutritional Diagnostic	body weight in kg	six months after collecting data from all research participants
Nutritional Diagnostic	height in m	six months after collecting data from all research participants
Nutritional Diagnostic	circumferences in cm	six months after collecting data from all research participants
Nutritional Diagnostic	body composition via triceps skin fold thickness in mm	six months after collecting data from all research participants
Nutritional Diagnostic	hand grip resistance assessed by dynamometry in kg	six months after collecting data from all research participants
Nutritional Diagnostic	Food Frequency Questionnaire	six months after collecting data from all research participants
Nutritional Diagnostic	24-hour recall	six months after collecting data from all research participants
Effect of the synbiotic in pain	Visual Analogue Score for Pain using the Visual Analogue Scale	six months after collecting data from all research participants
inflammatory marker	Blood samples for Tumor Necrosis Factor TNF in pg/mL	six months after collecting data from all research participants
inflammatory marker	Fatty Acid Binding Protein FABP2 in ng/mL	six months after collecting data from all research participants
inflammatory marker	Lipopolysaccharide Binding Protein LBP in µg/mL	six months after collecting data from all research participants
inflammatory marker	Lipopolysaccharide LPS in µg/mL	six months after collecting data from all research participants
inflammatory marker	leukogram White Blood Cell Count in cells/µL	six months after collecting data from all research participants
Questionnaire to assess quality of life	EORTC QLQ-C30 for all cancer patients	six months after collecting data from all research participants
Questionnaire to assess quality of life	EORTC QLQ-CR29 for colorectal cancer patients	six months after collecting data from all research participants

Collaborators and Investigators

• Sponsor: Federal University of Minas Gerais
• Investigators: Principal Investigator: Simone de Vasconcelos Generoso, Escola de Enfermagem - UFMG

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): December 12, 2025
• Study Completion (Estimated): December 12, 2026

Study Registration Dates

• First Submitted: May 11, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 27, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: colorectal cancer; chemotherapy; diarrhea; Mucositis; symbiotic
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis
• Other Study ID Numbers: 30177920200005149

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No