Treatment of Gastroesophageal Reflux Disease in Infants
- Conditions
- Infant, Newborn, DiseasesGastroesophageal Reflux
- Interventions
- Drug: Protein pump inhibitor. Continuing nutrition containing cows' milk protein.Behavioral: Mother or infant dietDrug: Placebo
- Registration Number
- NCT06255886
- Lead Sponsor
- Odense University Hospital
- Brief 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)
- Detailed 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 & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 96
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Proton pump inhibitor Protein pump inhibitor. Continuing nutrition containing cows' milk protein. Omeprazole 1 mg/ kg and continuing nutrition containing cow's milk protein Mother or infant diet Mother or infant diet Mother on cow milk-protein-free diet if breastfeeding and infant on a hypoallergenic formula if bottle-fed. Placebo Placebo Placebo medicine (appearing substantially like Omeprazole) 1mg/kg and continuing nutrition containing cow's milk protein
- Primary Outcome Measures
Name Time Method Change from baseline in reflux episodes Baseline and daily in 4 weeks. 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.
- Secondary Outcome Measures
Name Time Method Change from baseline in weight Baseline and 4 weeks A nurse or physician will perform the measurement on a weight in the clinic/hospital. Measurement unit: gram.
Change from baseline in the number of reflux episodes with visible blood 1,2,3,4 weeks Parent reported weekly number of reflux episodes with visible blood. Registered in MyCap App.
Change from baseline in the numbers of episodes with crying 1,2,3,4 weeks Parent reported weekly numbers of episodes with crying 5 minutes after feeding. Registered in MyCap App
Change from baseline in the number of episodes of refusing breast/ bottle 1,2,3,4 weeks Parent reported weekly numbers of episodes of refusing breast/bottle. Registered in MyCap App
Immunoglobulin E level 4 weeks after treatment is started Blood positive/negative for specific immunoglobulin E for cows milk protein. Values above 0,35 kU/l are considered positive for cows' milk allergy.
Change from baseline in the number of episodes with discomfort 1,2,3,4 weeks Parent reported weekly episodes with discomfort 5 min after feeding. Registered in MyCap App
Change from baseline in the number of episodes with short breathing pauses 1,2,3,4 weeks Parent-reported weekly numbers of episodes with short breathing pauses. Registered in MyCap App
Change from baseline in the number of episodes with troublesome breathing/cough 1,2,3,4 weeks Parent reported weekly numbers of episodes with troublesome breathing/cough. Registered in MyCap App
Change from baseline in the number of episodes with paleness/blue color in face or lips 1,2,3,4 weeks Parent reported weekly numbers of episodes with paleness/blue color in face. Registered in MyCap App