Treatment of Gastroesophageal Reflux Disease in Infants

Gastroesophageal Reflux Clinical Trial

Official title:

Treatment of Gastroesophageal Reflux Disease in Infants- a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06255886
• Other study ID #: OUH-HCA006
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 1, 2024
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: Odense University Hospital
• Contact: Natalia K Barkholt, MD
• Phone: +45 50276171
• Email: Natalia.Barkholt[@]rsyd.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gastroesophageal reflux disease in infants is not fully understood. Infants are prescribed medical treatments that may not be effective or that contribute to adverse side effects and lead to concerns and expenses for the parents and healthcare system. Current guidelines recommend cow-milk-protein free diet as a first-line treatment, but these recommendations are based on weak evidence. This study investigate the efficacy of a cow-milk-protein free diet compared to treatment with a proton pump inhibitor (omeprazole)

Description:

An increasing number of infants less than one year of age have been referred to the pediatric departments with gastroesophageal reflux in the past decade. Gastroesophageal reflux is a common condition in infants defined as the passage of gastric contents into the esophagus with regurgitation or vomiting. Around 50% of infants younger than four months regurgitate or vomit regularly. In most cases, it is a harmless, self-limiting condition; in 90% of cases, the symptoms diminish before 12 months. However, if reflux leads to troublesome symptoms or complications, it is defined as gastroesophageal reflux disease. Troublesome symptoms may include failure to thrive, back arching, food refusal, regurgitation, and irritability. The prevalence of gastroesophageal reflux disease varies between studies. Infants can be treated medically, and proton pump Inhibitors have been recommended as the first choice. However, within the last few years, there has been concern among pediatricians that too many infants are unnecessarily treated with this medication. There are only a few randomized studies on proton pump inhibitor treatment in children under one year, and most studies do not show a significant effect on symptoms. Side effects of treatment with proton pump inhibitors include symptoms related to the gastrointestinal tract or airways, increased susceptibility to infections, and increased risk of developing allergy later in life. Within the past years, there has been attention to the overlapping of symptoms between gastroesophageal reflux disease and allergy to cow milk protein. Cow-milk-protein allergy is the most common food allergy in early childhood, with an estimated prevalence of 2-3%, and presents with various symptoms predominantly from the skin and gastrointestinal tract. Consequently, cow-milk-protein allergy can be challenging to differentiate from gastroesophageal reflux disease. Cow-milk-protein-allergy is an immune reaction and can be either immunoglobulin E-mediated, presenting with immediate reaction including anaphylaxis, or non-immunoglobulin E-mediated, presenting with delayed symptoms. In addition, it is possible that cow's milk can aggravate gastroesophageal reflux disease with a non-immunologic mechanism. As there is no biomarker to differentiate non-immunoglobulin E-mediated cow-milk allergy from gastroesophageal reflux disease, the diagnosis of non-immunoglobulin E-mediated cow-milk allergy can only be verified by an oral food challenge test preceded by a cow-milk-protein-elimination period. Therefore, in the updated international guidelines, all children with gastroesophageal reflux disease should start with a 2-4-week cow-milk-protein-elimination diet before a proton pump inhibitor is prescribed. However, evidence is scarce on the effect of a cow-milk-protein-free diet in infants diagnosed with gastroesophageal reflux disease.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 1 Year

Eligibility

Inclusion Criteria:

• Infants diagnosed with gastroesophageal reflux disease (GERD)
• Age < 1 year at the time of referral
• Age >1 month at start of treatment
• At least 3 reflux episodes/daily in average
• At least one of following troublesome symptoms are present: Crying of unknown reason, discomfort/irritability, problems gaining weight/ weightloss, rejects the breast or bottle, apnea, back-arching.

Exclusion Criteria:

• Children with diagnosed or suspected syndrome /genetic disorder
• Congenital malformations (minor deformities are excepted)
• Abdominal surgery
• Metabolic disease
• Treatment with proton pump inhibitor within the last week
• Allergy for proton pump inhibitors
• Allergy for cow milk protein
• Infants on Cow's milk free diet

Related Conditions & MeSH terms

• Esophagitis, Peptic
• Gastroesophageal Reflux
• Infant, Newborn, Diseases

Intervention

Drug:
• Protein pump inhibitor. Continuing nutrition containing cows' milk protein.
1 mg/kg /day

Behavioral:
• Mother or infant diet
Mother on cow milk protein diet or infant on hypoallergenic formula in case of bottle fed

Drug:
• Placebo
Placebo medicine (appearing substantially like Omeprazole) 1mg/ ml, and continuing nutrition containing cows' milk protein

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Odense University Hospital	Hospital of Southern Jutland

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events to trial medicine in the proton pump inhibitor group and the placebo group	Any parent-reported adverse events to the trial medicine (both Omeprazole and placebo) are registered weekly.; There are several well-known side effects; 1-10 % experience symptoms from the gastrointestinal tract (i.e., stomach pain, nausea, and constipation), skin, airways, and increased susceptibility to infections.	1,2,3,4 weeks
Other	Cows milk allergy?	After 4 weeks´ of cows milk protein-free diet, an oral provocation test with cow's milk is conducted on all infants in the diet group, who experienced effect of the diet. The test will be carried out in the hospital. During the test, the infants are given increasing doses of fresh cow's milk every 30 minutes until they reach a maximum of 200 ml.; A nurse records any symptoms experienced during the first few hours of the test, and the parents are required to monitor and report any symptoms at home. Additionally, the parents inform the physician of any late symptoms via phone call 48 hours after the test.	4 weeks
Primary	Change from baseline in reflux episodes	Parent-reported reduction in the weekly number and size of reflux-episodes compared to placebo or the other active group, after four weeks of treatment. The outcome is registered daily in an App.	Baseline and daily in 4 weeks.
Secondary	Immunoglobulin E level	Blood positive/negative for specific immunoglobulin E for cows milk protein. Values above 0,35 kU/l are considered positive for cows' milk allergy.	4 weeks after treatment is started
Secondary	Change from baseline in weight	A nurse or physician will perform the measurement on a weight in the clinic/hospital. Measurement unit: gram.	Baseline and 4 weeks
Secondary	Change from baseline in the number of reflux episodes with visible blood	Parent reported weekly number of reflux episodes with visible blood. Registered in MyCap App.	1,2,3,4 weeks
Secondary	Change from baseline in the number of episodes with discomfort	Parent reported weekly episodes with discomfort 5 min after feeding. Registered in MyCap App	1,2,3,4 weeks
Secondary	Change from baseline in the numbers of episodes with crying	Parent reported weekly numbers of episodes with crying 5 minutes after feeding. Registered in MyCap App	1,2,3,4 weeks
Secondary	Change from baseline in the number of episodes of refusing breast/ bottle	Parent reported weekly numbers of episodes of refusing breast/bottle. Registered in MyCap App	1,2,3,4 weeks
Secondary	Change from baseline in the number of episodes with short breathing pauses	Parent-reported weekly numbers of episodes with short breathing pauses. Registered in MyCap App	1,2,3,4 weeks
Secondary	Change from baseline in the number of episodes with paleness/blue color in face or lips	Parent reported weekly numbers of episodes with paleness/blue color in face. Registered in MyCap App	1,2,3,4 weeks
Secondary	Change from baseline in the number of episodes with troublesome breathing/cough	Parent reported weekly numbers of episodes with troublesome breathing/cough. Registered in MyCap App	1,2,3,4 weeks