Clinical trial NCT06255886: Treatment of Gastroesophageal Reflux Disease in Infants
Official title: Treatment of Gastroesophageal Reflux Disease in Infants- a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Gastroesophageal Reflux
Infant, Newborn, Diseases
Keywords: Reflux
Infants
GERD
GER
GORD
GOR
Cow milk protein
Bovine milk protein
CMP
Proton pump inhibitor
PPI
Omeprazole
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Hospital of Southern Jutland
First posted: 2024-02-13
Enrollment: 96
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in reflux episodes
timeFrame: Baseline and daily in 4 weeks.
Secondary outcomes:
measure: Immunoglobulin E level
timeFrame: 4 weeks after treatment is started
measure: Change from baseline in weight
timeFrame: Baseline and 4 weeks
measure: Change from baseline in the number of reflux episodes with visible blood
timeFrame: 1,2,3,4 weeks
measure: Change from baseline in the number of episodes with discomfort
timeFrame: 1,2,3,4 weeks
measure: Change from baseline in the numbers of episodes with crying
timeFrame: 1,2,3,4 weeks
measure: Change from baseline in the number of episodes of refusing breast/ bottle
timeFrame: 1,2,3,4 weeks
measure: Change from baseline in the number of episodes with short breathing pauses
timeFrame: 1,2,3,4 weeks
measure: Change from baseline in the number of episodes with paleness/blue color in face or lips
timeFrame: 1,2,3,4 weeks
measure: Change from baseline in the number of episodes with troublesome breathing/cough
timeFrame: 1,2,3,4 weeks
Other outcomes:
measure: Adverse events to trial medicine in the proton pump inhibitor group and the placebo group
timeFrame: 1,2,3,4 weeks
measure: Cows milk allergy?
timeFrame: 4 weeks
Locations:
Study officials:
affiliation: H.C Andersen Childrens Hospital, Odense University Hospital and Syddansk University (SDU)
name: Gitte Zachariassen, Professor
role: STUDY_DIRECTOR
References: