AR Formula vs Omeprazole for Infant Acid Reflux

(GIFT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Sudarshan R [e-mail]

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Nationwide Children's Hospital

Must not be taking: Neuroactive medications

Disqualifiers: Chromosomal abnormalities, Congenital syndromes, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this investigator-initiated, single-center, randomized controlled trial (RCT) is to compare the effects of four weeks of three therapies on clinical and mechanistic outcomes based on pH-Imp testing using a three-arm parallel design in NICU infants with objective GERD diagnosis. The three therapies being compared are natural maturation, proton pump inhibitor (PPI) use, and added rice (AR) formula use. The main goals are: * to evaluate and compare the efficacy of the three commonly used treatment interventions used in the NICU for GERD in a randomized controlled manner with the primary endpoint of oral feeding success and absence of troublesome symptoms (as defined below). * to characterize the mechanisms of primary end point (success or failure) using pH-Impedance metrics.

Will I have to stop taking my current medications?

The trial requires that participants are not on any current GERD therapies, so you would need to stop taking any GERD medications before joining.

What data supports the effectiveness of the drug omeprazole for treating infant acid reflux?

Research shows that omeprazole, a proton pump inhibitor, is effective in relieving symptoms of gastroesophageal reflux disease (GERD) in children, with studies reporting a median symptom relief rate of 80.4%. It is well-tolerated and has a good safety profile in pediatric patients. ^{1 2 3 4 5}

Is omeprazole safe for use in humans?

Omeprazole, marketed under names like Losec, Prilosec, and Zegerid, is generally considered safe for human use and has been approved by the FDA for various conditions, including gastroesophageal reflux disease (GERD). However, Zegerid contains a high amount of sodium, which may not be suitable for everyone. ^{3 4 5 6 7}

How does the AR Formula and Omeprazole treatment for infant acid reflux differ from other treatments?

The AR Formula and Omeprazole treatment is unique because it combines a dietary approach (AR Formula, which is a thickened formula with added rice) with a medication (Omeprazole, a proton pump inhibitor that reduces stomach acid), offering a dual approach to managing infant acid reflux. This combination may provide both immediate physical relief from reflux through the thickened formula and longer-term acid reduction with Omeprazole, which is not typically seen in standard treatments that often focus on medication alone. ^{1 2 3 5 8}

Research Team

Sudarshan R [e-mail]

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

This trial is for NICU infants with a confirmed GERD diagnosis, who are on full enteral feeds and not currently receiving any GERD treatment. Infants must meet specific pH-impedance criteria to qualify.

Inclusion Criteria

I am not currently on any treatments for acid reflux.

Full enteral feeds

My baby is in the NICU, diagnosed with GERD based on specific tests.

Exclusion Criteria

I need surgery for a stomach or upper intestine problem.

I use a breathing aid with more than 4 liters per minute of air or oxygen.

I do not have any known lethal genetic disorders.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants are randomized to one of three therapies: natural maturation, proton pump inhibitor (PPI) use, or added rice (AR) formula use for 4 weeks.

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on oral feeding success and absence of GERD symptoms.

4 weeks

Treatment Details

Interventions

• AR formula (Behavioural Intervention)
• Omeprazole (Proton Pump Inhibitor)

Trial Overview The GIFT Trial compares three treatments for infant GERD over four weeks: natural growth without intervention, Omeprazole (a proton pump inhibitor), and AR formula feeding. The main focus is on successful oral feeding and the absence of troublesome symptoms.

Participant Groups

Group I: Proton Pump Inhibitor (PPI) Active Control 1 Intervention

Omeprazole will be prescribed for 4 weeks using the dose of 1.5mg/kg/dose daily.

Group II: Natural maturation Active Control 1 Intervention

Allows for time for infant maturation without treatment.

Group III: Added Rice (AR) Formula Active Control 1 Intervention

Added rice formula will be ordered as the infant diet for the 4-week treatment period.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Nationwide Children's Hospita Columbus, OH

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Patients Recruited

5,228,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2513

Patients Recruited

4,366,000+

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment. [2018] A substantial percentage of infants, children and adolescents experience gastroesophageal reflux disease (GERD) and its accompanying symptoms, as well as disease complications. The diagnosis of GERD in children is made based upon the child's history, and data derived primarily from pH monitoring tests and endoscopy. In those children with confirmed reflux disease, the options for management parallel those recommended in adult patients, with the first step consisting of lifestyle changes. Surgical procedures may also be performed; however, these are rarely recommended prior to an adequate course of pharmacologic therapy, and appropriate case selection is important. Among the current pharmacotherapeutic options available in the US, the prokinetic agents and the acid-inhibitory agents (histamine-2 receptor antagonists, proton pump inhibitors) are the most widely used. The clinical utility of the prokinetic agents has been limited by the recent withdrawal of cisapride from the US marketplace and the potential for irreversible central nervous system complications with metoclopramide. Numerous clinical studies performed in adults, and several studies involving children, have demonstrated that the proton pump inhibitors are more effective than the histamine-2 receptor antagonists in the relief of GERD symptoms and healing of erosive esophagitis. In children, omeprazole and lansoprazole may be administered as the intact oral capsule, or in those who are unable or unwilling to swallow, the granule contents of the capsule may be mixed with soft foods (e.g. apple sauce) or fruit drinks/liquid dietary supplements prior to oral administration with no detrimental effects on pharmacokinetics, bioavailability, or pharmacodynamics. Studies performed with omeprazole and lansoprazole in children have shown pharmacokinetic parameters that closely resemble those observed in adults. In over a decade of use in adults, the proton pump inhibitor class of agents has been found to have a good safety profile. Studies involving children have also shown these agents to be well tolerated. In numerous drug-drug interaction studies performed with these two proton pump inhibitors, relatively few clinically significant interactions have been observed.

2. New Zealand pubmed.ncbi.nlm.nih.gov

Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review. [2021] Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009) and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%-100%). Five studies reported a significant reduction of the esophageal reflux index within normal limits (

3. United States pubmed.ncbi.nlm.nih.gov

Omeprazole maintenance therapy for gastroesophageal reflux disease after failure of fundoplication. [2019] Recurrence of gastroesophageal reflux (GER) in children after failed fundoplication poses a therapeutic challenge. The authors report the experience with long-term omeprazole for children with severe GER after failed fundoplication.

4. Hungary pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two capsule formulations of omeprazole. [2013] Bioequivalency of Omeraz, a test-product of Arab Pharmaceutical Manufacturing Company (Jordan) and Losec, a reference product by Astra (Sweden), was evaluated by a randomised crossover study on 22 healthy male volunteers. Serum concentrations of omeprazole were measured by an HPLC assay. There were no statistically significant differences between the two products in terms of serum profile and pharmacokinetic parameters including AUC, Cmax, Tlag, Tmax, MRT, Ke and T1/2. The AUC ratios (Omeraz/Losec) for 24 hours and for infinity were respectively 1.02 with a 90% C.L. of 0.88-1.16 and 1.00 with a 90% C.L. of 0.88-1.14. The two products may be considered as bioequivalent in terms of the extent of absorption as indicated by the AUC ratios. However, the confidence limits of Cmax fall outside the FDA accepted range.

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. [2022] To evaluate the efficacy and safety of proton pump inhibitors in infants aged

6. United States pubmed.ncbi.nlm.nih.gov

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec. [2020] Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD).

7. United States pubmed.ncbi.nlm.nih.gov

Zegerid--immediate-release omeprazole. [2013] The FDA has approved marketing of Zegerid powder for oral suspension (Santarus), an immediate-release formulation of the proton-pump inhibitor (PPI) omeprazole (Prilosec, and others). All other oral PPIs are delayed-release, enteric-coated formulations designed to prevent degradation of the drug by gastric acid. Each 20- or 40-mg packet of Zegerid contains 1680 mg sodium bicarbonate, which protects the drug from gastric acid degradation. A dose of Zegerid contains 460 mg of sodium, which may be excessive for some patients. Zegerid is the first oral PPI to be approved by the FDA for reduction of risk of upper GI bleeding in critically ill patients. The drug may be useful for patients who are unable to swallow and have nasogastric (NG) tubes in place. Zegerid cost $70.00 for 14 days' treatment, compared to less than $10 for 14 tablets of Prilosec OTC.

8. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants with symptomatic GERD. [2015] : The efficacy and safety of rabeprazole, a proton pump inhibitor, were studied in infants with gastroesophageal reflux disease (GERD).