A "Screen and Treat" Helicobacter Pylori Eradication Trial in Adolescents in Three Regions of Chile

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-02

Study Completion Date

2027-03-31

Brief Summary

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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 up to 1000 asymptomatic adolescents 14-18 years of age from 3 cities of Chile (Colina, Temuco and Coyhaique), to find a total of 210 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

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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 96.8% 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 disease/damage. 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 up to 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. 210 Subjects with persistent infection will then be randomized 2:1 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.

Conditions

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Helicobacter Pylori Infection

Keywords

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Helicobacter pylori Screen and treat Pepsinogen Adolescent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Screening phase: 14-18-year-old students (up to 1000) from three cities will be invited. After obtaining informed consent, eligible participants without exclusion criteria will undergo an H. pylori screening test (Urea Breath Test; UBT). Those negative will exit, except for a subset to be followed as a non-infected controls. Subjects with a positive test will undergo two confirmatory tests 30 days apart to confirm infection persistence. Approximately 20-25% are expected to be positive.

Intervention phase: those with persistent H. pylori infection will undergo gastroenterological evaluation 1 month before randomization (2:1) to receive antimicrobial treatment or no treatment. Non-infected controls will be followed at matched intervals. If untreated, subjects with persistent infection will be offered the eradication regimen after completing the initial 6-month follow-up with blood and stool samples taken.

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Blinded Gastroenterologist or trained physician who performs the surveillance after eradication treatment. No other parties will be masked in the clinical trial.

Study Groups

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Cases

140 children with H. pylori-persistent infection, who will receive eradication therapy

Group Type EXPERIMENTAL

Lansoprazole

Intervention Type DRUG

14 days of Lansoprazole (30 mg BID) (days 1-14)

Amoxicillin

Intervention Type DRUG

7 days of Amoxicillin (1000 mg BID) (days 1-7)

Clarithromycin

Intervention Type DRUG

7 days of Clarithromycin (500 mg BID) (days 8-14)

Metronidazole

Intervention Type DRUG

7 days of Metronidazole (500 mg BID) (days 8-14)

Controls

70 children with H. pylori-persistent infection, who will not receive eradication therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Non infected Controls

60 adolescents with no H. pylori infection, they will not receive eradication therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Lansoprazole

14 days of Lansoprazole (30 mg BID) (days 1-14)

Intervention Type DRUG

Amoxicillin

7 days of Amoxicillin (1000 mg BID) (days 1-7)

Intervention Type DRUG

Clarithromycin

7 days of Clarithromycin (500 mg BID) (days 8-14)

Intervention Type DRUG

Metronidazole

7 days of Metronidazole (500 mg BID) (days 8-14)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Healthy teenagers 14-18 years of age from Colina, Temuco or Coyhaique
2. At least one responsible adult family member accessible for phone contact.
3. Persistent H. pylori infection determined by at least 2 positive UBT tests in a 3 months period (except for Non-infected Controls)

Exclusion Criteria

1. Teenagers not consenting to treatment will be invited to continue as non-treated controls.
2. Known allergy to any of the antimicrobials used in the trial protocol (except for Non-infected Controls)
3. Signs/symptoms compatible with organic abdominal pain according to Rome IV criteria: persistent right upper or right lower quadrant pain, dysphagia, odynophagia, persistent vomiting, gastrointestinal blood loss, involuntary weight loss, deceleration of linear growth, delayed puberty.
4. Prior eradication therapy
5. Antimicrobial course received during the previous month (at least 3 days of treatment at appropriate dosing, children meeting this criteria can be included at a later stage)
6. Pregnancy
7. Use of immunosuppressive or biologic drugs
8. Children deemed "not healthy" after review of the questionnaire by study physician

Minimum Eligible Age

14 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Responsible Party

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Miguel O'Ryan Gallardo

Medical Doctor, Pediatrician, Infectious Diseases Specialist. Full Professor.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Miguel O'Ryan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chile

Locations

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Universidad de Aysén

Coyhaique, , Chile

Site Status RECRUITING

Universidad de Chile

Santiago, , Chile

Site Status RECRUITING

Universidad de la Frontera

Temuco, , Chile

Site Status RECRUITING

Countries

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Chile

Central Contacts

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Yalda Lucero, MD, PhD

Role: CONTACT

Phone: +56229786658

Email: [email protected]

Sergio George, MD, PhD

Role: CONTACT

Phone: +56225756103

Email: [email protected]

Facility Contacts

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Beatriz Zabala, PhD

Role: primary

Sergio George, MD, PhD

Role: primary

Lilian Fernández, MD

Role: primary

References

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O'Ryan ML, Lucero Y, Rabello M, Mamani N, Salinas AM, Pena A, Torres-Torreti JP, Mejias A, Ramilo O, Suarez N, Reynolds HE, Orellana A, Lagomarcino AJ. Persistent and transient Helicobacter pylori infections in early childhood. Clin Infect Dis. 2015 Jul 15;61(2):211-8. doi: 10.1093/cid/civ256. Epub 2015 Apr 2.

Reference Type BACKGROUND

PMID: 25838286 (View on PubMed)

O'Ryan ML, Rabello M, Cortes H, Lucero Y, Pena A, Torres JP. Dynamics of Helicobacter pylori detection in stools during the first 5 years of life in Chile, a rapidly developing country. Pediatr Infect Dis J. 2013 Feb;32(2):99-103. doi: 10.1097/INF.0b013e318278b929.

Reference Type BACKGROUND

PMID: 23076385 (View on PubMed)

Lucero Y, Lagomarcino AJ, Torres JP, Roessler P, Mamani N, George S, Huerta N, Gonzalez M, O'Ryan M. Helicobacter pylori, clinical, laboratory, and noninvasive biomarkers suggestive of gastric damage in healthy school-aged children: A case-control study. Int J Infect Dis. 2021 Feb;103:423-430. doi: 10.1016/j.ijid.2020.11.202. Epub 2020 Dec 2.

Reference Type BACKGROUND

PMID: 33278617 (View on PubMed)

Lucero Y, Lagomarcino AJ, Torres JP, Roessler P, Mamani N, George SA, Huerta N, Gonzalez M, O'Ryan G M. Effect of Helicobacter pylori eradication therapy on clinical and laboratory biomarkers associated with gastric damage in healthy school-aged children: A randomized non-blinded trial. Helicobacter. 2021 Dec;26(6):e12853. doi: 10.1111/hel.12853. Epub 2021 Sep 15.

Reference Type BACKGROUND

PMID: 34528337 (View on PubMed)

George S, Lucero Y, Cabrera C, Zabala Torres B, Fernandez L, Mamani N, Lagomarcino A, Aguilera X, O'Ryan M. Protocol for a randomised 'screen-and-treat' Helicobacter pylori eradication trial in 14-18-years-old adolescents residing in three regions of Chile: effectiveness and microbiological host implications. BMJ Open. 2025 Jan 30;15(1):e084984. doi: 10.1136/bmjopen-2024-084984.

Reference Type DERIVED

PMID: 39890135 (View on PubMed)

Other Identifiers

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1220964

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1220964

Identifier Type: -

Identifier Source: org_study_id

A "Screen and Treat" Helicobacter Pylori Eradication Trial in Adolescents in Three Regions of Chile

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Cases

Lansoprazole

Amoxicillin

Clarithromycin

Metronidazole

Controls

Non infected Controls

Interventions

Lansoprazole

Amoxicillin

Clarithromycin

Metronidazole

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Fondo Nacional de Desarrollo Científico y Tecnológico, Chile

Miguel O'Ryan Gallardo

Responsible Party

Miguel O'Ryan Gallardo

Principal Investigators

Miguel O'Ryan, MD

Locations

Universidad de Aysén

Universidad de Chile

Universidad de la Frontera

Countries

Central Contacts

Yalda Lucero, MD, PhD

Sergio George, MD, PhD

Facility Contacts

Beatriz Zabala, PhD

Sergio George, MD, PhD

Lilian Fernández, MD

References

O'Ryan ML, Rabello M, Cortes H, Lucero Y, Pena A, Torres JP. Dynamics of Helicobacter pylori detection in stools during the first 5 years of life in Chile, a rapidly developing country. Pediatr Infect Dis J. 2013 Feb;32(2):99-103. doi: 10.1097/INF.0b013e318278b929.

Other Identifiers

1220964

1220964