Stopping GERD Therapy for Children with Cystic Fibrosis

Overseen By Shatha Yousef, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must be taking: GERD medications

Disqualifiers: Severe GERD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Baseline

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether children with Cystic Fibrosis (CF) can safely discontinue their reflux (GERD) medication. Researchers aim to track symptom changes after stopping the treatment by using a survey to monitor how the children feel. The trial targets children aged 6-17 who have CF and have maintained a steady dose of GERD medication for at least three months, without severe reflux issues. Participants must be willing to stop their GERD therapy, such as Proton Pump Inhibitors or H2 Receptor Antagonists, for the study. As an unphased trial, this study offers a unique opportunity to contribute to understanding the impact of stopping GERD medication in children with CF.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your GERD medications to participate in this trial.

What prior data suggests that discontinuing GERD therapy is safe for children with Cystic Fibrosis?

Research has shown that proton pump inhibitors (PPIs), commonly used to treat gastroesophageal reflux disease (GERD), are generally safe for children. Most side effects are mild, typically involving digestive issues or skin reactions. Studies indicate that serious side effects are rare, so stopping PPI treatment is usually unnecessary due to safety concerns. However, PPIs have been linked to some risks, such as an increased chance of asthma or reduced bone strength in children. Despite these potential risks, the overall safety of PPIs in children remains favorable, and discontinuing the treatment is not expected to cause major safety issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the possibility of safely discontinuing GERD therapy in children with cystic fibrosis who don't have severe GERD symptoms. Unlike current treatments for GERD, which typically involve long-term use of medications to reduce stomach acid, this approach investigates if stopping therapy could maintain symptom control without ongoing medication. This could potentially reduce medication burden, side effects, and healthcare costs for these patients. The trial aims to understand if children can maintain their health and quality of life without continuous GERD treatment, which would be a significant shift in managing GERD in the context of cystic fibrosis.

What evidence suggests that discontinuing GERD therapy might be effective for children with Cystic Fibrosis?

Research has shown that stopping acid reflux treatment in children with cystic fibrosis might be beneficial in some cases. This trial will have participants discontinue GERD therapy to assess its impact. Studies have found that acid blockers, such as proton pump inhibitors (PPIs), can affect growth and disrupt the balance of gut bacteria in young children with cystic fibrosis. This disruption can potentially lead to issues like lower hemoglobin levels, which are crucial for oxygen transport in the blood. Although acid blockers were often used early in life, their long-term benefits and effects remain unclear. Therefore, discontinuing acid reflux treatment might help avoid these potential negative effects, but careful monitoring of the child is essential. ^{2 6 7 8 9}

Who Is on the Research Team?

Shatha Yousef

Principal Investigator

Duke University Hospital

Are You a Good Fit for This Trial?

This trial is for children with Cystic Fibrosis who are currently receiving treatment for Gastroesophageal Reflux Disease (GERD). The study aims to include those who can provide symptom feedback via a survey.

Inclusion Criteria

Signed consent

I am currently taking medication for acid reflux.

My GERD medication dose has been the same for the last 3 months.

Exclusion Criteria

GSAS score >80

I do not wish to join the study or sign the consent form.

Unwillingness to stop GERD therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete the GSAS survey at baseline while on GERD therapy

Baseline

1 visit (in-person)

Observation

GERD therapy is discontinued, and symptoms are monitored using the GSAS survey

12 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Discontinuation of GERD therapy

Trial Overview The study focuses on understanding the impact of stopping GERD therapy in children with Cystic Fibrosis. It involves monitoring changes in reflux symptoms through patient surveys after discontinuing treatment.

How Is the Trial Designed?

Group I: Child with CF on GERD therapy without severe GERD Experimental Treatment 1 Intervention

The GSAS will be completed at baseline, GERD therapy will be discontinued, and GSAS will be repeated 12 weeks later.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Cystic Fibrosis Foundation

Collaborator

Trials

199

Recruited

37,800+

Published Research Related to This Trial

Proton pump inhibitors (PPIs) are effective in healing erosive esophagitis and improving symptoms of gastroesophageal reflux disease (GERD) in children, as supported by multiple studies.

While short-term use of PPIs is generally well tolerated with mild-to-moderate adverse effects, including headaches, the long-term safety and efficacy in young children, particularly infants under 12 months, require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety and efficacy of proton pump inhibitors in paediatric gastroesophageal reflux disease. Kierkus, J., Oracz, G., Korczowski, B., et al.[2021]

In a study of 126 cystic fibrosis patients using proton pump inhibitors (PPIs) for at least 6 months, there was a significant increase in pulmonary exacerbations, with 59.6% of PPI users experiencing them compared to only 24.5% in the control group.

While hypomagnesemia was more common in PPI users (16.7%) compared to the control group (2%), the difference was not statistically significant, indicating a potential safety concern that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and Incidence of Adverse Effects of Proton Pump Inhibitors in Patients with Cystic Fibrosis. McCrory, BE., Harper, HN., McPhail, GL.[2021]

Proton pump inhibitors (PPIs) like omeprazole and lansoprazole are more effective than histamine-2 receptor antagonists for treating gastroesophageal reflux disease (GERD) in children, with studies showing they effectively relieve symptoms and heal erosive esophagitis.

PPIs have a good safety profile in both adults and children, with minimal clinically significant drug interactions, and can be administered in various forms to accommodate children who have difficulty swallowing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment. Gold, BD., Freston, JW.[2018]

In a study of 114 cystic fibrosis patients, those who used proton pump inhibitors (PPIs) had a significantly higher mean number of hospitalizations for pulmonary exacerbations, with an average of 1.4 hospitalizations compared to 0.9 for non-users.

The association between PPI use and increased hospitalizations remained significant even after controlling for other risk factors, indicating that PPI therapy may pose additional risks for patients with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Pump Inhibitor Use Is Associated With an Increased Frequency of Hospitalization in Patients With Cystic Fibrosis. Ayoub, F., Lascano, J., Morelli, G.[2022]

A study analyzing 70 reports of adverse drug reactions (ADRs) related to proton pump inhibitors (PPIs) in children found that most ADRs were not serious, with gastrointestinal and skin issues being the most common.

Serious ADRs occurred more frequently when PPIs were used in combination with other medications, highlighting the importance of monitoring for potential interactions in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions related to proton pump inhibitors in pediatric population: an analysis of spontaneous reporting data. Dipasquale, V., Cicala, G., Laganà, F., et al.[2022]

Lansoprazole was well tolerated in a study involving 48 pediatric patients under 1 year of age, with only a few mild to moderate treatment-related adverse events reported after 5 days of treatment.

The medication effectively increased intragastric pH levels and reduced the frequency of GERD symptoms, such as regurgitation and vomiting, indicating its efficacy in managing GERD in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacodynamics of lansoprazole in patients with gastroesophageal reflux disease aged Springer, M., Atkinson, S., North, J., et al.[2022]

In a study of 166 pediatric patients using proton pump inhibitors (PPIs) for over 9 months, the median duration of use was 3 years, with some patients taking them for up to 11 years, primarily for gastroesophageal reflux disease (GERD) and related disorders.

The study found that while 79% of patients had GERD-predisposing conditions, only a few adverse reactions were reported, suggesting that long-term PPI use in children is generally safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of children receiving proton pump inhibitors continuously for up to 11 years duration. Hassall, E., Kerr, W., El-Serag, HB.[2013]

Proton pump inhibitors (PPIs) do not significantly reduce symptoms associated with gastroesophageal reflux disease (GERD) in infants under 1 year of age, despite their effectiveness in adults.

The largest trial indicated that infants treated with PPIs experienced a higher rate of adverse events compared to those on placebo, highlighting concerns about the safety of PPIs in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Higginbotham, TW.[2010]

In a study of 160 patients with cystic fibrosis, prolonged use of proton pump inhibitors (PPIs) for at least 3 months did not lead to significant improvements in nutritional status, as measured by changes in BMI z-score.

However, the use of PPIs was associated with an increased risk of respiratory infections, specifically a rise in positive cultures for Pseudomonas aeruginosa, suggesting that caution is warranted when prescribing PPIs to these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prolonged proton pump inhibitor treatment on nutritional status and respiratory infection risk in cystic fibrosis: A matched cohort study. Zazzeron, L., Alicandro, G., Daccò, V., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11615133/

Impact of acid blocker therapy on growth, gut microbiome ... We examined associations between ABT usage and growth, gut microbiome (GM), and early‐onset lung disease in young children with CF.

2. link.springer.com link.springer.com/article/10.1007/s10620-024-08728-8

Proton-Pump Inhibitors and Fat Absorption in Cystic ... This was a pilot randomized, double-blind, placebo-controlled crossover trial of subjects aged 12 and older with CF and EPI assessed on placebo and omeprazole.

3. mdpi.com mdpi.com/2227-9067/11/3/296

Proton Pump Inhibitors in Pediatric Gastroesophageal ... For children and adolescents, PPIs were effective in improving symptoms and achieving endoscopic healing, which was subsequently maintained. To conclude, PPIs ...

4. cfdb.eu cfdb.eu/en/topics/detail/code/032

Topic :: Agents which reduce gastric acidity in cystic fibrosis Main results showed that ABT before age 3 years was frequent, with 81 (56%) of patients on H2 receptor antagonist (H2RA) or proton pump ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8217294/

USE OF PROTON PUMP INHIBITORS IS ASSOCIATED ... Males and females with CF who used PPIs and females with CF who concurrently used PPIs and H2RAs had lower Hgb levels than never-users of ASMs of the same sex.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10969042/

Proton Pump Inhibitors in Pediatric Gastroesophageal ... PPIs are considered safe drugs, with most of the reported adverse events (AEs) being mild and related to digestive symptoms or skin reactions [ ...

7. jpeds.com jpeds.com/article/S0022-3476(06)01190-5/fulltext

Characteristics of Children Receiving Proton Pump ... Few adverse reactions to these drugs occur, and discontinuation of the drug is seldom indicated. These preliminary data suggest that PPIs may be efficacious and ...

8. researchgate.net researchgate.net/publication/383496038_A_review_of_proton_pump_inhibitor_use_in_cystic_fibrosis_and_considerations_for_deprescribing

A review of proton pump inhibitor use in cystic fibrosis and ... BACKGROUND: Acid suppression therapy (AST), including proton pump inhibitors ... No children discontinued because of adverse events or safety findings. In ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06617013

NCT06617013 | GERD in Children With Cystic Fibrosis The purpose of this study is to use a survey to measure reflux symptoms in patients with Cystic Fibrosis who are on reflux treatment, and to monitor their ...