Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06560879
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-06
Brief Title:
Effectiveness of Probiotics for the Prevention of Gastrointestinal Toxicity in Children With Leukemia
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effectiveness of Probiotics for the Prevention of Gastrointestinal Toxicity and Changes in Gut Microbiota in Children With Acute Lymphoblastic Leukemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 325 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
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
Detailed Description:
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 531 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 77 to 325 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
1 Participant selection and consent
Participants meeting the study selection criteria will be selected
Informed consent will be obtained from the participants parents or guardians and if appropriate from the patient if older than 8 years of age They will be informed about the benefits complications and adverse effects of the interventions Appendix 1-3
If the parents or guardians prefer treatment outside the research project the patient will be treated according to the established national protocols used in the Oncology Service of the Instituto Nacional de Pediatría
Consent will also be obtained for the use of personal data as per Appendices 4 and 5 This data includes participant and parent names birth date sex CURP address contact number medical history general habits pathological conditions social conditions to be used exclusively for this research project
Data will be handled with strict confidentiality stored in an electronic database for five years by project personnel
2 Initial Assessments
A pediatric oncologist will perform a medical history physical examination anthropometry fecal and serum sampling
A nutritionist will evaluate the participants nutritional status and body composition
A Physical examination
Participant will remove outer clothing and shoes and sit on the examination table
The pediatric oncologist will visually inspect for skin lesions using a lamp and tongue depressor if necessary
Body temperature will be measured with a digital thermometer
Participants will lie supine for palpation percussion andor auscultation to assess cardiac and abdominal conditions
B Anthropometry
Weight will be measured three times using a Seca scale
Height will be measured three times using a stadiometer
Waist circumference will be measured at the midpoint between the lower edge of the last rib and the upper edge of the iliac crest
Hip circumference will be measured 15 cm below the waist
Arm circumference will be measured around the biceps muscle
Thigh circumference will be measured around the upper third of the thigh
C Nutritional Status
- Height-for-Age H-A Weight-for-Age W-A Weight-for-Height W-H and Body Mass Index BMI indices will be classified according to NOM-008-SSA2-1993 standards
D Body composition
Participants will remove metallic objects empty their bladder and lie supine on a non-conductive bed
Electrode placement will be prepared with a cleansing towel and an electrically conductive towel
Electrodes will be placed on hands and feet and a multifrequency bioelectric impedance device will measure body composition at six different frequencies
Data will be adjusted to WHO percentile curves
E Fecal samples
Participants will collect stool samples at home using provided kits and instructions
Samples will be transported in a cooler to the Instituto Nacional de Pediatría on the same day for analysis and will be stored in the freezer at -70C until the end of the project
F Serum samples
A 3 ml blood sample will be collected by peripheral venipuncture
Serum samples will be processed to determine antibodies against beta-lactoglobulin using the sandwich enzyme immunoassay technique
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
3 Preparation of interventions
Interventions will be prepared in a Baker Company Class II Type A2 vertical laminar flow hood
The required amounts of lyophilized probiotic powder and microcrystalline cellulose will be mixed for 5 minutes 230 clockwise and 230 counterclockwise at a speed of 25 rpm and encapsulated at a dose of L casei and L rhamnosus at 25 billion CFU per capsule B bifidum at 1 billion CFU per capsule and placebo 300 mg of microcrystalline cellulose
Each intervention will be stored in labeled sterile bags and refrigerated at 2 to 8C
Capsules will be quality checked for UFC content at Bacteriology Laboratory by dilution and sequencing and any deviations will result in process adjustments
4 Participant Allocation
Participants will be randomly assigned to interventions using a computer-generated sequence adjust in balanced blocks of five Appendix 7
An external researcher will place intervention names in opaque envelopes labeled with random numbers of the sequence
Participants will draw a random number to be assigned to an intervention communicated to the principal investigator
5 Intervention Administration
Participants will receive bottles with 14-16 capsules of the assigned intervention stored in a cooler with refrigerated gel packs
Participants will take one capsule before breakfast and one before lunch for one week recording adherence in a logbook and repeating this process for eight weeks
6 Clinical Evaluation
- Weekly clinical evaluations will be conducted for mucositis diarrhea colitis flatulence abdominal distention and constipation graded according to the Common Terminology Criteria for Adverse Events CTCAE scale V 402 39 If necessary the pediatric oncologist will initiate treatment according to the Oncology service plan
7 Data Collection
If antibiotics are required or the chemotherapy consolidation phase is completed participants will be eliminated from the study and final assessments will be conducted
Data from weekly clinical evaluations nutritional assessments and study follow-ups will be recorded in a data collection form Appendix 8 and entered an electronic Excel database for statistical analysis using STATA 18 by a blinded researcher
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 005 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 Petos 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
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
1 Participant selection and consent
Participants meeting the study selection criteria will be selected
Informed consent will be obtained from the participants parents or guardians and if appropriate from the patient if older than 8 years of age They will be informed about the benefits complications and adverse effects of the interventions Appendix 1-3
If the parents or guardians prefer treatment outside the research project the patient will be treated according to the established national protocols used in the Oncology Service of the Instituto Nacional de Pediatría
Consent will also be obtained for the use of personal data as per Appendices 4 and 5 This data includes participant and parent names birth date sex CURP address contact number medical history general habits pathological conditions social conditions to be used exclusively for this research project
Data will be handled with strict confidentiality stored in an electronic database for five years by project personnel
2 Initial Assessments
A pediatric oncologist will perform a medical history physical examination anthropometry fecal and serum sampling
A nutritionist will evaluate the participants nutritional status and body composition
A Physical examination
Participant will remove outer clothing and shoes and sit on the examination table
The pediatric oncologist will visually inspect for skin lesions using a lamp and tongue depressor if necessary
Body temperature will be measured with a digital thermometer
Participants will lie supine for palpation percussion andor auscultation to assess cardiac and abdominal conditions
B Anthropometry
Weight will be measured three times using a Seca scale
Height will be measured three times using a stadiometer
Waist circumference will be measured at the midpoint between the lower edge of the last rib and the upper edge of the iliac crest
Hip circumference will be measured 15 cm below the waist
Arm circumference will be measured around the biceps muscle
Thigh circumference will be measured around the upper third of the thigh
C Nutritional Status
- Height-for-Age H-A Weight-for-Age W-A Weight-for-Height W-H and Body Mass Index BMI indices will be classified according to NOM-008-SSA2-1993 standards
D Body composition
Participants will remove metallic objects empty their bladder and lie supine on a non-conductive bed
Electrode placement will be prepared with a cleansing towel and an electrically conductive towel
Electrodes will be placed on hands and feet and a multifrequency bioelectric impedance device will measure body composition at six different frequencies
Data will be adjusted to WHO percentile curves
E Fecal samples
Participants will collect stool samples at home using provided kits and instructions
Samples will be transported in a cooler to the Instituto Nacional de Pediatría on the same day for analysis and will be stored in the freezer at -70C until the end of the project
F Serum samples
A 3 ml blood sample will be collected by peripheral venipuncture
Serum samples will be processed to determine antibodies against beta-lactoglobulin using the sandwich enzyme immunoassay technique
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
3 Preparation of interventions
Interventions will be prepared in a Baker Company Class II Type A2 vertical laminar flow hood
The required amounts of lyophilized probiotic powder and microcrystalline cellulose will be mixed for 5 minutes 230 clockwise and 230 counterclockwise at a speed of 25 rpm and encapsulated at a dose of L casei and L rhamnosus at 25 billion CFU per capsule B bifidum at 1 billion CFU per capsule and placebo 300 mg of microcrystalline cellulose
Each intervention will be stored in labeled sterile bags and refrigerated at 2 to 8C
Capsules will be quality checked for UFC content at Bacteriology Laboratory by dilution and sequencing and any deviations will result in process adjustments
4 Participant Allocation
Participants will be randomly assigned to interventions using a computer-generated sequence adjust in balanced blocks of five Appendix 7
An external researcher will place intervention names in opaque envelopes labeled with random numbers of the sequence
Participants will draw a random number to be assigned to an intervention communicated to the principal investigator
5 Intervention Administration
Participants will receive bottles with 14-16 capsules of the assigned intervention stored in a cooler with refrigerated gel packs
Participants will take one capsule before breakfast and one before lunch for one week recording adherence in a logbook and repeating this process for eight weeks
6 Clinical Evaluation
- Weekly clinical evaluations will be conducted for mucositis diarrhea colitis flatulence abdominal distention and constipation graded according to the Common Terminology Criteria for Adverse Events CTCAE scale V 402 39 If necessary the pediatric oncologist will initiate treatment according to the Oncology service plan
7 Data Collection
If antibiotics are required or the chemotherapy consolidation phase is completed participants will be eliminated from the study and final assessments will be conducted
Data from weekly clinical evaluations nutritional assessments and study follow-ups will be recorded in a data collection form Appendix 8 and entered an electronic Excel database for statistical analysis using STATA 18 by a blinded researcher
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 005 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 Petos 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None