Ignite Creation Date:
2024-05-06 @ 7:11 PM
Last Modification Date:
2024-10-26 @ 3:02 PM
Study NCT ID:
NCT05926804
Status:
RECRUITING
Last Update Posted:
2024-01-05
First Post:
2023-06-01
Brief Title:
A Screen and Treat Helicobacter Pylori Eradication Trial in Adolescents in Three Regions of Chile
Sponsor:
Miguel ORyan Gallardo
Organization:
University of Chile
Study Overview
Official Title:
A Screen and Treat Helicobacter Pylori Eradication Trial in 14-18 Years Old Adolescents Residing in Three Regions of Chile Effectiveness and Microbiological-host Implications
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Gastric cancer remains a global health problem and Chile has one of the highest GC mortality rates in the region Helicobacter pylori H pylori infection is ubiquitous in Chilean adults and it constitutes the main cause of GC worldwide A long-term process occurs from premalignant lesions to carcinoma H pylori eradication during early stages of disease significantly impacts outcomes favoring survival disease reversal and molecular changes which supports a screen and treat strategy in asymptomatic populations in areas with intermediate-to-high GC prevalence The Investigators previous research has shown that H pylori infection is acquired in early childhood with low rates of spontaneous eradication A pilot treatment study in a subset of school-aged asymptomatic children showed a high rate of successful eradication 95 good tolerance and was associated with a decrease in serum biomarkers of gastric damage pepsinogen I and II Based on the results of these studies the Investigators propose to advance towards the next stage of this research process a screen and treat strategy The current trial starts with a Screening phase testing 1000 asymptomatic adolescents 14-18 years of age from 3 cities of Chile Colina Temuco and Coyhaique to find a total of 200-250 persistently-infected participants Persistently-infected adolescents will be included in a Second phase of this trial A randomized case-control non-blinded study to either receive antimicrobial treatment targeting H pylori eradication cases or no treatment controls A subset of 60 non-infected adolescents will be followed-up in matched times This aims to provide evidence on the effect of treatment on clinical outcomes and serum biomarkers related to gastric damage as well as composition and antimicrobial resistance of gut microbiota The Investigators expect that eradication therapy will be successful in 90 of persistently infected adolescents with reinfection rates not surpassing 15 in a 2-3 year period and to be associated with a decrease in clinical findings indicative of gastric disease and a decrease in serum biomarker indicative of gastric damage
Detailed Description:
Background Helicobacter pylori H pylori infection is the main cause of gastric cancer GC and long-term process occurs from premalignant lesions to carcinoma H pylori eradication during early stages of disease in young adults screen and treat significantly impacts GC favoring survival disease reversal and molecular changes Effects of eradication therapy in affecting gut microbiome diversity and composition and increasing antibiotic resistance rates in commensal bacteria appear to be transient in most studies The investigators have shown that infection is acquired mainly during the first 5 years of life most infected children remain persistently infected with low rates of spontaneous eradication and persistently infected children have more abdominal complaints and higher levels of pepsinogen PG II marker of gastric damage A pilot eradication trial in persistently infected school-aged children showed that with sequential triple therapy eradication was achieved in 968 of children and treated children had a decrease in PG I and II levels compared to non-treated The Investigators propose a screen and treat strategy aimed at a transition age between childhood and adulthood in areas with intermediate-high gastric cancer prevalence to assess efficacy of eradication its clinical and molecular benefits and potential microbial side effects Aims The primary aim will be to determine the effectiveness of H pylori eradication therapy in 14-18 years old adolescents in three regions with nearly 20-25 persistence rates and determine the effect of eradication on clinical and serum biomarkers of gastric diseasedamage The secondary aims will be to determine the effects of H pylori eradication therapy on antimicrobial resistance of potentially pathogenic enteric bacteria and on gut microbiome composition Exploratory aims To determine the presence of clarithromycin resistance genes in H pylori by stool analysis of children not achieving eradication and determine the effects of reinfection on clinical findings indicative of gastric disease and biomarkers indicative of gastric damage gut microbiota composition and antimicrobial resistance of H pylori and other potentially pathogenic bacteria Methods The Investigators will invite through contact with the health and educational authorities of Colina Temuco and Coyhaique 14-18 year old students until we reach 1000 adolescents enrolled H pylori screening test Urea Breath Test UBT will be offered and adolescents with a positive test will undergo two additional tests separated by 30 days in order to confirm infection persistence at least two positive tests It is expected that 20-25 of adolescents screened to be positive for H pylori of which over 90 will be persistently infected Subjects will then be randomized 21 to receive either an antimicrobial course targeting H pylori eradication 7 days of lansoprazole and amoxicillin followed by 7 days of lansoprazole and clarithromycin plus metronidazole or no treatment Participants will be followed-up with UBT 1 month post treatment and then every 6 months for the remaining surveillance period gastroenterological evaluation 2 weeks pre treatment 1 month 3 months 9 months and 18 months post treatment blood samples and stool samples 2 weeks pre-treatment 1 month and 6 months post treatment A subset of 60 non-infected students from each site will be followed-up in matched times To those subjects with persistent infection who do not receive treatment the same eradication regimen will be offered after they have completed the initial 6-month follow-up with their blood and stool samples taken
Serum gastric damage biomarkers will be assessed using GastroPanel PGI PGII Gastrin and ELISA commercial kits VCAM-1 CXCL13 Escherichia coli and Enterococcus spp will be cultured from stools samples and resistance to 6 antimicrobials will be assessed by disk diffusion method H pylori clarithromycin resistance gene will be amplified from stools using nested-qPCR Composition of gut microbiome will be characterized by amplification and sequencing the 16SrRNA gene from stools ant then bioinformatics analysis Expected results The prevalence of persistent H pylori infection will be around 20-25 in adolescents from Colina Coyhaique and Temuco Eradication will be successful in 90 of persistently infected students and reinfection rates will not surpass 15 in a 2-3 year period Eradication will be significantly associated with a decrease in clinical findings indicative of gastric disease and a decrease in biomarker levels indicative of gastric damage Treatment will have a transitory effect on increasing antimicrobial resistance rates of potentially pathogen enteric bacteria Escherichia coli Enterococcus spp Treatment will have a transitory effect on disrupting gut microbiota composition at phylum class order family and genus levels which will be restored to levels comparable to non-infected healthy teenagers at the end of follow-up In those adolescents for whom eradication therapy fails clarithromycin resistance will be more prevalent in pretreatment samples compared to those eradicating H pylori in reinfected children treatment will have a transitory effect on increasing detection rates of H pylori clarithromycin resistance genes
Serum gastric damage biomarkers will be assessed using GastroPanel PGI PGII Gastrin and ELISA commercial kits VCAM-1 CXCL13 Escherichia coli and Enterococcus spp will be cultured from stools samples and resistance to 6 antimicrobials will be assessed by disk diffusion method H pylori clarithromycin resistance gene will be amplified from stools using nested-qPCR Composition of gut microbiome will be characterized by amplification and sequencing the 16SrRNA gene from stools ant then bioinformatics analysis Expected results The prevalence of persistent H pylori infection will be around 20-25 in adolescents from Colina Coyhaique and Temuco Eradication will be successful in 90 of persistently infected students and reinfection rates will not surpass 15 in a 2-3 year period Eradication will be significantly associated with a decrease in clinical findings indicative of gastric disease and a decrease in biomarker levels indicative of gastric damage Treatment will have a transitory effect on increasing antimicrobial resistance rates of potentially pathogen enteric bacteria Escherichia coli Enterococcus spp Treatment will have a transitory effect on disrupting gut microbiota composition at phylum class order family and genus levels which will be restored to levels comparable to non-infected healthy teenagers at the end of follow-up In those adolescents for whom eradication therapy fails clarithromycin resistance will be more prevalent in pretreatment samples compared to those eradicating H pylori in reinfected children treatment will have a transitory effect on increasing detection rates of H pylori clarithromycin resistance genes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1220964 | OTHER_GRANT | Fondecyt Fondo Nacional de Desarrollo Científico y Tecnológico | None |