Cystic FibrosisNCT02769637
Effect of Acid Blockade on Microbiota and Inflammation in Cystic Fibrosis (CF)
An observational study of Cystic Fibrosis, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
Mucus in the airways of patients with CF represents an area for bacteria proliferation, microbial infection and inflammation. Similar to the lung, the esophagus provides an environment for bacterial to grow. Read more about this study
- Who is it for?
- Ages 10 to 21 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- PPI treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Sep 2017to 18 Jan 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 10 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Subjects with Cystic Fibrosis
Who may be able to join
- Ages 10-21 years
- Known diagnosis of CF based on sweat chloride > 60 mEq/L or identification of two known Cystic fibrosis transmembrane conductance regulator (CFTR) mutations
- Clinically stable pulmonary disease defined by
- clinical impression of patient's primary CF provider,
- no newly prescribed antibiotic treatments in the 30 days prior to enrollment, and
- relativly stable lung function with a forced expiratory volume in 1 second (FEV1) within 10% of baseline.
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- Male and female
- Willing to participate in and comply with all study procedures, and
- Willingness of the subject, parent or legally authorized representative to provide written informed consent.
- Body Mass Index (BMI) >25%
- >40% FEV1.
- Willing to stop acid blockade medication for 6 weeks for aim 1.
- Not on acid blockade for 6 weeks for aim 2.
Who cannot join
- FEV1 less than 40% predicted
- History of meconium ileus, distal intestinal obstructive syndrome, gastrointestinal surgery, or intestinal stricture.
- CF liver disease with cirrhosis, gastric or esophageal varices.
- Unwilling to participate in and comply with the study procedures.
- Unwillingness of the subject, parent or legally authorized representative to provide written informed consent.
- Unwilling or unable to swallow the capsule with the esophageal string test (EST).
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- Gelatin allergy.
- History of esophageal surgery including fundoplication, or
- Presence of a gastrostomy tube.
- Confirmed or suspected diagnosis of Gastroesophageal Reflux Disease (GERD)
- BMI < 25%
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Mucus in the airways of patients with CF represents an area for bacteria proliferation, microbial infection and inflammation. Similar to the lung, the esophagus provides an environment for bacterial to grow. The overall goal of this proposal is to characterize the esophageal microbiota of children with CF that are treated or untreated with acid blockade medication and to measure its possible impact on respiratory disease to develop novel treatment strategies.
Read the detailed description
Patients with cystic fibrosis (CF) have significant morbidity and mortality due to airway infections. These infections are related to the deficiency of mucociliary clearance due to thick dehydrated secretions. Thus, considerable effort is spent managing airway infections. This includes therapies to improve mucus clearance and antibiotic treatments that target important pathogens. Understanding the source of airway microbiota, increased risk of infection, and exacerbation is critical to improve management of airway infection. A large proportion of CF patients are also treated with anti-acid medications. These medications decrease symptoms associated with gastroesophageal reflux disease (GERD), and improve the efficacy of enzyme replacement therapies. Critical for this proposal is the fact that aspiration may represent a potential route for airway infection from microorganisms in the upper gastrointestinal (GI) tract, and anti-acid treatments shift the GI microbiota. In preliminary studies we have identified a strong alteration of the esophageal microbiota in subjects using acid blocking medications. Thus, these treatments may have a significant effect on the bacterial communities present in the upper GI tract and may play a role in infection and exacerbation in CF. Traditionally, access to the upper GI tract has required endoscopy to acquire biopsy tissue, which is an invasive procedure and not routinely performed in CF. To circumvent the invasive sampling required for study of the esophagus we have recently shown that a minimally invasive test, the esophageal string test (EST), is capable of sampling the upper GI tract, and has performance comparable to biopsy for a number of measurements including assessment of the esophageal microbiota.
The primary hypothesis for this proposal is that acid blockade medication alters the esophageal microbiota in CF, increasing the presence of pathogenic bacteria and inflammation. To test this hypothesis we propose three Specific Aims:
Specific aim 1: Determine whether esophageal microbial composition in children with CF changes after withdrawal of acid blockade
- Comparison of esophageal bacterial load by 16S qPCR in subjects on acid blockade and after withdrawal
- Examine the stability of the esophageal bacterial communities based on longitudinal collection of the esophageal string test (EST) prior to withdrawal of acid blockade treatment.
- Determine if there are changes after withdrawal of acid blockade in both sputum microbiota composition and esophageal microbiota (including presence of pathogenic bacteria) and whether the changes are correlated across the two sample types.
Specific aim 2: Determine whether esophageal microbiota in children with CF changes after initiation of acid blockade in patients started for clinical indications
- Comparison of esophageal bacterial load by 16S qPCR of the esophageal bacteria in subjects pre and post acid blockade treatment.
- Examine the stability of the esophageal bacterial communities based on longitudinal collection of the esophageal string test (EST) prior to acid blockade treatment initiation.
- Determine if there are changes after initiation of acid blockade in both sputum microbiota composition and esophageal microbiota (including presence of pathogenic bacteria) and whether the changes are correlated across the two sample types.
Specific aim3: Examine the relation between acid blockade medication and inflammation in association with bacterial communities in subjects from aim 1 and 2
- CompareIL-8 in the esophagus in subjects with and without acid blockade
- Compare IL-8 in the sputum in subjects with and without acid blockade and determine relation between inflammation and association with shifts in the bacterial communities.
Together, these aims will provide novel information regarding the impact of acid blockade treatment on the esophageal and lung microbiota that may impact management of respiratory disease in CF. We anticipate similar effects of acid blockade on the esophageal bacterial communities as we observed in non-CF pediatric and adult subjects, but acknowledge that treatment burden in CF, particularly antibiotics, may affect the expected outcome. These data will provide critical information to evaluate the effect of acid blockade on infection risk, which could affect therapeutic choices for patients with CF. The long-term goal of these studies, is to improve patient care by assessing the effect of acid blocker therapy on the microbiota and inflammation.
- Conditions
- Cystic Fibrosis
- Being tested
- PPI treatment
- Keywords
- upper gastrointestinal tract, lung microbiota and inflammation
- Medical subject headings
- Cystic Fibrosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PPI treatmentDrug
Also called Acid blockade medication
PPI treatment or no PPI treatment
| Study group | Role | What they receive |
|---|---|---|
| ON PPI | Subjects on proton pump inhibitor (PPI) treatment Receives: Drug: PPI treatment | |
| OFF PPI | Subjects off proton pump inhibitor (PPI) treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the microbiota and inflammation
Identification of bacterial communities and IL-8
Measured: Baseline and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study start7 Sep 2017
- Primary completion18 Jan 2018
- Study completion18 Jan 2018
Why it stopped: unable to meet the target enrollment goal
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Sophie Fillon, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02769637
- Sponsor's protocol ID
- 16-0672
- Status last verified
- Jun 2018
- First submitted
- 10 May 2016
- Last updated
- 27 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Acid Blockade on Microbiota and Inflammation in Cystic Fibrosis (CF)
- ClinicalTrials.gov ID
- NCT02769637
- Acronym / sponsor ID
- 16-0672
- Conditions
- Cystic Fibrosis
- Keywords
- upper gastrointestinal tract, lung microbiota and inflammation
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: unable to meet the target enrollment goal
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 18 Jan 2018 (actual)
- Study completion
- 18 Jan 2018 (actual)
- First posted
- 11 May 2016 (estimated)
- 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.
Mucus in the airways of patients with CF represents an area for bacteria proliferation, microbial infection and inflammation. Similar to the lung, the esophagus provides an environment for bacterial to grow. The overall goal of this proposal is to characterize the esophageal microbiota of children with CF that are treated or untreated with acid blockade medication and to measure its possible impact on respiratory disease to develop novel treatment strategies.
Detailed description
Patients with cystic fibrosis (CF) have significant morbidity and mortality due to airway infections. These infections are related to the deficiency of mucociliary clearance due to thick dehydrated secretions. Thus, considerable effort is spent managing airway infections. This includes therapies to improve mucus clearance and antibiotic treatments that target important pathogens. Understanding the source of airway microbiota, increased risk of infection, and exacerbation is critical to improve management of airway infection. A large proportion of CF patients are also treated with anti-acid medications. These medications decrease symptoms associated with gastroesophageal reflux disease (GERD), and improve the efficacy of enzyme replacement therapies. Critical for this proposal is the fact that aspiration may represent a potential route for airway infection from microorganisms in the upper gastrointestinal (GI) tract, and anti-acid treatments shift the GI microbiota. In preliminary studies we have identified a strong alteration of the esophageal microbiota in subjects using acid blocking medications. Thus, these treatments may have a significant effect on the bacterial communities present in the upper GI tract and may play a role in infection and exacerbation in CF. Traditionally, access to the upper GI tract has required endoscopy to acquire biopsy tissue, which is an invasive procedure and not routinely performed in CF. To circumvent the invasive sampling required for study of the esophagus we have recently shown that a minimally invasive test, the esophageal string test (EST), is capable of sampling the upper GI tract, and has performance comparable to biopsy for a number of measurements including assessment of the esophageal microbiota.
The primary hypothesis for this proposal is that acid blockade medication alters the esophageal microbiota in CF, increasing the presence of pathogenic bacteria and inflammation. To test this hypothesis we propose three Specific Aims:
Specific aim 1: Determine whether esophageal microbial composition in children with CF changes after withdrawal of acid blockade
- Comparison of esophageal bacterial load by 16S qPCR in subjects on acid blockade and after withdrawal
- Examine the stability of the esophageal bacterial communities based on longitudinal collection of the esophageal string test (EST) prior to withdrawal of acid blockade treatment.
- Determine if there are changes after withdrawal of acid blockade in both sputum microbiota composition and esophageal microbiota (including presence of pathogenic bacteria) and whether the changes are correlated across the two sample types.
Specific aim 2: Determine whether esophageal microbiota in children with CF changes after initiation of acid blockade in patients started for clinical indications
- Comparison of esophageal bacterial load by 16S qPCR of the esophageal bacteria in subjects pre and post acid blockade treatment.
- Examine the stability of the esophageal bacterial communities based on longitudinal collection of the esophageal string test (EST) prior to acid blockade treatment initiation.
- Determine if there are changes after initiation of acid blockade in both sputum microbiota composition and esophageal microbiota (including presence of pathogenic bacteria) and whether the changes are correlated across the two sample types.
Specific aim3: Examine the relation between acid blockade medication and inflammation in association with bacterial communities in subjects from aim 1 and 2
- CompareIL-8 in the esophagus in subjects with and without acid blockade
- Compare IL-8 in the sputum in subjects with and without acid blockade and determine relation between inflammation and association with shifts in the bacterial communities.
Together, these aims will provide novel information regarding the impact of acid blockade treatment on the esophageal and lung microbiota that may impact management of respiratory disease in CF. We anticipate similar effects of acid blockade on the esophageal bacterial communities as we observed in non-CF pediatric and adult subjects, but acknowledge that treatment burden in CF, particularly antibiotics, may affect the expected outcome. These data will provide critical information to evaluate the effect of acid blockade on infection risk, which could affect therapeutic choices for patients with CF. The long-term goal of these studies, is to improve patient care by assessing the effect of acid blocker therapy on the microbiota and inflammation.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ON PPI | – | Drug: PPI treatmentSubjects on proton pump inhibitor (PPI) treatment |
| OFF PPI | – | –Subjects off proton pump inhibitor (PPI) treatment |
Who may qualify
- Ages
- 10 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Subjects with Cystic Fibrosis
Key inclusion criteria (13 listed)
- Ages 10-21 years
- Known diagnosis of CF based on sweat chloride > 60 mEq/L or identification of two known Cystic fibrosis transmembrane conductance regulator (CFTR) mutations
- Clinically stable pulmonary disease defined by
- Male and female
- Willing to participate in and comply with all study procedures, and
Key exclusion criteria (11 listed)
- FEV1 less than 40% predicted
- History of meconium ileus, distal intestinal obstructive syndrome, gastrointestinal surgery, or intestinal stricture.
- CF liver disease with cirrhosis, gastric or esophageal varices.
- Unwilling to participate in and comply with the study procedures.
- Unwillingness of the subject, parent or legally authorized representative to provide written informed consent.
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 |
|---|---|---|
| PPI treatmentAlso: Acid blockade medicationPPI treatment or no PPI treatment | Drug | ON PPI |
Primary outcome
Changes in the microbiota and inflammation
Time frame: Baseline and 6 weeks
Identification of bacterial communities and IL-8
Results and safety
The study was stopped early (reason given: unable to meet the target enrollment goal). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Sophie Fillon, PhD principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by University of Colorado, Denver at 2 sites in United States.
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 13 inclusion and 11 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: stopped early, as of the sponsor's last update on 27 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
The study was stopped early (reason given: unable to meet the target enrollment goal). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the microbiota and inflammation (time frame: Baseline and 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2018.