Proton Pump InhibitorsPPINCT07036627
Intestinal Microbiota After PPI Treatment
An observational study of Proton Pump Inhibitors and Human Gastrointestinal Tract, run by University of Bari at 1 site in Italy.
Trial summary
This clinical study aims to investigate the effects of short-term treatment with proton pump inhibitors (PPIs) on the gut microbiota of pediatric patients. PPIs are among the most frequently prescribed medications in children and adolescents for the management of acid-related disorders, such as gastroesophageal reflux… Read more about this study
- Who is it for?
- Ages 6 months to 17 years
- Conditions the study is for
- Proton Pump Inhibitors, Human Gastrointestinal Tract, Gastroesophageal Reflux Disease
- What is being tested?
- study of microbiota
- Type of treatment
- Pill or oral medicine
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 6 Jul 2025to 1 Feb 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Population with GERD
Who may be able to join
- Male or female children and adolescents aged between 6 months and 17 years at the time of enrollment.
- Clinical indication for proton pump inhibitor therapy, including but not limited to gastroesophageal reflux disease, esophagitis, or functional dyspepsia.
- Willingness and ability of the child and their caregivers to comply with all study procedures, including collection of fecal samples at scheduled time points.
- Written informed consent obtained from a parent or legal guardian; assent obtained from the child, when age-appropriate, in accordance with local regulations and ethical standards.
Who cannot join
- Use of systemic antibiotics, antifungals, or probiotics within 30 days prior to the start of the study or during the observation period.
- Incomplete or improperly handled stool sample collection, or failure to adhere to protocol-defined sampling windows.
- Known diagnosis of primary immunodeficiency, inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or celiac disease.
- Any condition that, in the opinion of the investigator, may interfere with the integrity of the study or pose additional risks to the participant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Evaluation of the Intestinal Microbiota in Pediatric Patients Treated With Proton Pump Inhibitors: A Prospective Longitudinal Study
This clinical study aims to investigate the effects of short-term treatment with proton pump inhibitors (PPIs) on the gut microbiota of pediatric patients. PPIs are among the most frequently prescribed medications in children and adolescents for the management of acid-related disorders, such as gastroesophageal reflux disease (GERD). However, emerging evidence suggests that these medications may have unintended consequences on the delicate ecosystem of beneficial microorganisms residing in the human gastrointestinal tract.
The intestinal microbiota plays a pivotal role in modulating immune responses, supporting nutrient metabolism, and maintaining the integrity of the gut barrier. Disruption of this microbial balance-known as dysbiosis-has been associated with several health conditions, including infections, allergies, obesity, and chronic inflammation. In adults, long-term PPI use has been linked to microbiota alterations, but data in the pediatric population remain limited and inconclusive.
Read more
To address this gap, our prospective longitudinal study will recruit pediatric patients prescribed PPI therapy for clinical indications. Stool samples will be collected at four time points: prior to PPI administration, during treatment, and at two follow-up stages post-cessation. Using 16S rRNA gene sequencing, we will profile changes in microbial diversity and abundance over time.
The results will offer insight into whether short-term PPI exposure in children leads to significant, lasting changes in gut microbiota composition or diversity. Such information may ultimately inform prescribing practices, support personalized therapeutic strategies, and help mitigate potential risks associated with microbiota disruption during childhood-a critical period for microbial and immune system development.
- Being tested
- study of microbiota
- Keywords
- PPI, GERD, microbiota, gastroesophageal reflux
- Medical subject headings
- Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
study of microbiotaOther
- Drug: Esomeprazole, a proton pump inhibitor commonly used in pediatric gastroenterology.
- Administration: Oral, once daily, 30 minutes before meals.
- Dosage: Personalized dosing according to body weight, with an average of approximately 0.6 mg/kg/day.
- Treatment duration: Minimum 45 days, maximum 60 days.
- Comparator: None. This is a within-subject design; each participant serves as their own control with baseline samples (t0) compared to follow-up (t1-t2).
- Monitoring: Adherence to therapy and sample collection timeline will be verified during scheduled clinical follow-up.
| Study group | Role | What they receive |
|---|---|---|
| PPI | PPI Receives: Other: study of microbiota |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in microbiota
- Definition: Change in the relative abundance of key bacterial families (Streptococcaceae, Ruminococcaceae, Clostridiales, etc.) from t0 to t1.
- Methodology: High-throughput 16S rRNA gene sequencing (regions V3-V4) using the Illumina MiSeq platform; taxonomic assignment via the SILVA reference database.
- Justification: These bacterial families have been previously associated with dysbiosis and PPI-related shifts in microbial composition.
Measured: 60 days from baseline
Secondary outcomes (1)
Microbial diversity
- Alpha-diversity: Within-sample microbial diversity measured by Shannon's entropy and Chao1 richness estimator.
- Beta-diversity: Between-sample differences using Bray-Curtis dissimilarity; visualized via principal coordinates analysis (PCoA).
- Differential abundance: Identification of statistically enriched or depleted taxa using LEfSe (Linear Discriminant Analysis Effect Size).
- Clinical correlation: Incidence of gastrointestinal (e.g., diarrhea, abdominal pain) and respiratory symptoms (e.g., cough, wheezing) reported during or after therapy.
Measured: 60 days from baseline.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2025
- Study start6 Jul 2025 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Proton Pump InhibitorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bari
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ruggiero Francavilla, University of Bari
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07036627
- Sponsor's protocol ID
- PPI
- Acronym
- PPI
- Status last verified
- Jun 2025
- First submitted
- 16 Jun 2025
- Last updated
- 29 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatr. 2018 Jun 4;172(6):e180315. doi: 10.1001/jamapediatrics.2018.0315. Epub 2018 Jun 4.
PubMed 29610864Simakachorn L, Tanpowpong P, Chanprasertyothin S, Thongpradit S, Treepongkaruna S. Gut Microbiota Characteristics in Children After the Use of Proton Pump Inhibitors. Turk J Gastroenterol. 2021 Jan;32(1):70-75. doi: 10.5152/tjg.2020.20245.
PubMed 33893768Raisanen L, Viljakainen H, Kolho KL. Exposure to proton pump inhibitors is associated with the development of pediatric autoimmune diseases. Front Pediatr. 2023 Mar 27;11:1157547. doi: 10.3389/fped.2023.1157547. eCollection 2023.
PubMed 37051434Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020 Aug;109(8):1531-1538. doi: 10.1111/apa.15213. Epub 2020 Mar 18.
PubMed 32027402Zhang YJ, Connearney S, Hester L, Du M, Catacora A, Akkara A, Wen A, Bry L, Alm EJ, Rosen R. Longitudinal Microbiome Changes in Children Exposed to Proton Pump Inhibitors. Clin Transl Gastroenterol. 2024 Sep 1;15(9):e1. doi: 10.14309/ctg.0000000000000703.
PubMed 38624107Liu C, Bach TR, Farrell PM, Pavelec D, Antos NJ, Rock MJ, Asfour F, Howenstine M, Gaffin JM, Lai HJ. Impact of acid blocker therapy on growth, gut microbiome, and lung disease in young children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2024 Dec;79(6):1124-1133. doi: 10.1002/jpn3.12389. Epub 2024 Oct 28.
PubMed 39465618
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Intestinal Microbiota in Pediatric Patients Treated With Proton Pump Inhibitors: A Prospective Longitudinal Study
- ClinicalTrials.gov ID
- NCT07036627
- Acronym / sponsor ID
- PPI / PPI
- Keywords
- PPI, GERD, microbiota, gastroesophageal reflux
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of BariUniversity, hospital or other
- Study start
- 6 Jul 2025 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 25 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study aims to investigate the effects of short-term treatment with proton pump inhibitors (PPIs) on the gut microbiota of pediatric patients. PPIs are among the most frequently prescribed medications in children and adolescents for the management of acid-related disorders, such as gastroesophageal reflux disease (GERD). However, emerging evidence suggests that these medications may have unintended consequences on the delicate ecosystem of beneficial microorganisms residing in the human gastrointestinal tract.
The intestinal microbiota plays a pivotal role in modulating immune responses, supporting nutrient metabolism, and maintaining the integrity of the gut barrier. Disruption of this microbial balance-known as dysbiosis-has been associated with several health conditions, including infections, allergies, obesity, and chronic inflammation. In adults, long-term PPI use has been linked to microbiota alterations, but data in the pediatric population remain limited and inconclusive.
To address this gap, our prospective longitudinal study will recruit pediatric patients prescribed PPI therapy for clinical indications. Stool samples will be collected at four time points: prior to PPI administration, during treatment, and at two follow-up stages post-cessation. Using 16S rRNA gene sequencing, we will profile changes in microbial diversity and abundance over time.
The results will offer insight into whether short-term PPI exposure in children leads to significant, lasting changes in gut microbiota composition or diversity. Such information may ultimately inform prescribing practices, support personalized therapeutic strategies, and help mitigate potential risks associated with microbiota disruption during childhood-a critical period for microbial and immune system development.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PPI | – | Other: study of microbiotaPPI |
Who may qualify
- Ages
- 6 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Population with GERD
Key inclusion criteria (4 listed)
- Male or female children and adolescents aged between 6 months and 17 years at the time of enrollment.
- Clinical indication for proton pump inhibitor therapy, including but not limited to gastroesophageal reflux disease, esophagitis, or functional dyspepsia.
- Willingness and ability of the child and their caregivers to comply with all study procedures, including collection of fecal samples at scheduled time points.
- Written informed consent obtained from a parent or legal guardian; assent obtained from the child, when age-appropriate, in accordance with local regulations and ethical standards.
Key exclusion criteria (4 listed)
- Use of systemic antibiotics, antifungals, or probiotics within 30 days prior to the start of the study or during the observation period.
- Incomplete or improperly handled stool sample collection, or failure to adhere to protocol-defined sampling windows.
- Known diagnosis of primary immunodeficiency, inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or celiac disease.
- Any condition that, in the opinion of the investigator, may interfere with the integrity of the study or pose additional risks to the participant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| study of microbiota* Drug: Esomeprazole, a proton pump inhibitor commonly used in pediatric gastroenterology. * Administration: Oral, once daily, 30 minutes before meals. * Dosage: Personalized dosing according to body weight, with an average of approximately 0.6 mg/kg/day. * Treatment duration: Minimum 45 days, maximum 60 days. * Comparator: None. This is a within-subject design; each participant serves as their own control with baseline samples (t0) compared to follow-up (t1-t2). * Monitoring: Adherence to therapy and sample collection timeline will be verified during scheduled clinical follow-up. | Other | PPI |
Primary outcome
Changes in microbiota
Time frame: 60 days from baseline
* Definition: Change in the relative abundance of key bacterial families (Streptococcaceae, Ruminococcaceae, Clostridiales, etc.) from t0 to t1. * Methodology: High-throughput 16S rRNA gene sequencing (regions V3-V4) using the Illumina MiSeq platform; taxonomic assignment via the SILVA reference database. * Justification: These bacterial families have been previously associated with dysbiosis and PPI-related shifts in microbial composition.
1 secondary outcome
Microbial diversity
Time frame: 60 days from baseline.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2025.
- Results publication: PubMed 29610864Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatr. 2018 Jun 4;172(6):e180315. doi: 10.1001/jamapediatrics.2018.0315. Epub 2018 Jun 4.
- Results publication: PubMed 33893768Simakachorn L, Tanpowpong P, Chanprasertyothin S, Thongpradit S, Treepongkaruna S. Gut Microbiota Characteristics in Children After the Use of Proton Pump Inhibitors. Turk J Gastroenterol. 2021 Jan;32(1):70-75. doi: 10.5152/tjg.2020.20245.
- Results publication: PubMed 37051434Raisanen L, Viljakainen H, Kolho KL. Exposure to proton pump inhibitors is associated with the development of pediatric autoimmune diseases. Front Pediatr. 2023 Mar 27;11:1157547. doi: 10.3389/fped.2023.1157547. eCollection 2023.
- Results publication: PubMed 32027402Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020 Aug;109(8):1531-1538. doi: 10.1111/apa.15213. Epub 2020 Mar 18.
- Results publication: PubMed 38624107Zhang YJ, Connearney S, Hester L, Du M, Catacora A, Akkara A, Wen A, Bry L, Alm EJ, Rosen R. Longitudinal Microbiome Changes in Children Exposed to Proton Pump Inhibitors. Clin Transl Gastroenterol. 2024 Sep 1;15(9):e1. doi: 10.14309/ctg.0000000000000703.
- Results publication: PubMed 39465618Liu C, Bach TR, Farrell PM, Pavelec D, Antos NJ, Rock MJ, Asfour F, Howenstine M, Gaffin JM, Lai HJ. Impact of acid blocker therapy on growth, gut microbiome, and lung disease in young children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2024 Dec;79(6):1124-1133. doi: 10.1002/jpn3.12389. Epub 2024 Oct 28.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Proton Pump Inhibitors and Human Gastrointestinal Tract, run by University of Bari at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruggiero Francavilla, Prof (00390805592063, ruggiero.francavilla@uniba.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in microbiota (time frame: 60 days from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07036627, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2025.