Cow's Milk Protein Allergy
Conditions
Keywords
Amino Acid Formula, Extended Hydrolyzed Formula, Cow's milk protein allergy
Brief summary
This clinical trial aims to evaluate and compare the efficacy of amino acid formula (AAF) and extensively hydrolyzed formula (eHF) in relieving symptoms in infants suspected of cow's milk protein allergy (CMPA) during the diagnostic elimination diet phase. The study will also assess treatment compliance, economic costs, and develop a CMPA screening score suitable for Chinese infants. Eligible infants (0-6 months old) will be randomized to receive either AAF or eHF for at least 2 weeks. Symptom improvement will be evaluated, followed by an oral food challenge (OFC) to confirm CMPA diagnosis. Infants in the eHF group who do not improve may switch to AAF for further evaluation. The total duration of participation is approximately 6 to 8 weeks. The study aims to provide evidence-based data to optimize diagnostic pathways and improve quality of life for infants with CMPA.
Detailed description
Cow's milk protein allergy (CMPA) is one of the most common food allergies in infants, with a prevalence of approximately 2.5-3.0% globally and 0.83-3.5% in China. Accurate diagnosis is often challenging due to the non-specific and variable symptoms, which may involve gastrointestinal, dermatologic, or respiratory systems. The current diagnostic gold standard involves an elimination diet followed by an oral food challenge (OFC). However, the choice of formula during the elimination phase may affect both symptom relief and diagnostic accuracy. This multicenter, randomized, open-label controlled trial (DREAM-CHINA) is designed to evaluate the clinical efficacy of two hypoallergenic formulas-amino acid formula (AAF) and extensively hydrolyzed formula (eHF)-in the diagnostic elimination diet phase for infants suspected of having CMPA. The study also aims to compare the two formulas in terms of symptom improvement rate, economic burden, treatment compliance, and formula acceptance. A total of 320 infants aged 0-6 months with suspected CMPA will be enrolled and randomized (1:1) to receive either AAF or eHF for at least 2 weeks. Infants whose symptoms significantly improve will undergo an OFC to confirm the diagnosis. Those in the eHF group who do not show improvement may switch to AAF for an additional 2 weeks before undergoing OFC. Record the speed of symptom improvement after eliminating the diet, and evaluate the diagnosis rate of CMPA through OFC, the time of symptom improvement, safety results, and the effectiveness of symptom-based screening tools for CMPA in Chinese infants. Throughout the study, data will be collected via electronic diaries (eCOA), clinical assessments, and standardized symptom scoring tools (e.g., CoMiSS). Regular follow-ups will monitor anthropometric growth, symptom progression, and adverse events. This study seeks to provide high-quality evidence for optimizing clinical decision-making and improving the diagnostic process for CMPA in Chinese infants.
Interventions
DIETARY_SUPPLEMENTAmino Acid Formula (AAF)
A formula composed of 100% free amino acids with no intact cow's milk protein. Participants will be fed AAF ad libitum according to their nutritional needs. Daily intake and symptoms will be recorded through an electronic diary (eCOA).
DIETARY_SUPPLEMENTExtensively Hydrolyzed Formula (eHF)
A formula in which cow's milk proteins are broken down into small peptides through enzymatic hydrolysis, reducing allergenicity. Participants will be fed eHF ad libitum based on their nutritional needs. Intake and symptoms will be tracked through an electronic diary (eCOA).
Sponsors
Ruijin Hospital
Guangzhou Women and Children's Medical Center
Beijing Children's Hospital
Peking University Third Hospital
Guangdong Provincial People's Hospital
Chengdu Women's and Children's Central Hospital
Guiyang Maternity and Child Health Care Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Masking Description
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to receive either an amino acid formula (AAF) or an extensively hydrolyzed formula (eHF) during the diagnostic elimination diet phase. Both groups will follow at least 2 weeks of formula-based feeding. Infants in the eHF group who do not show symptom improvement may switch to AAF for another 2 weeks. Symptom improvement will be evaluated to determine eligibility for an oral food challenge (OFC) to confirm the diagnosis of cow's milk protein allergy (CMPA).
Eligibility
Sex/Gender
ALL
Age
0 Months to 6 Months
Healthy volunteers
No
Inclusion criteria
* Infants aged 0-6 months; * Diagnosed with suspected CMPA at the time of presentation; * Artificially or mixed-feeding; * Parents willing to sign a written informed consent and comply with the study - protocol.
Exclusion criteria
* Infants currently receiving eHF or AAF formula; * Mixed-feeding infants whose current daily formula intake is less than 50% of their total milk intake or less than 200 ml; * Infants who have already started adding complementary foods; * Infants who have experienced severe food allergy symptoms such as shock, severe vomiting, etc. after taking cow's milk protein; * Infants with clinical manifestations of systemic allergic reaction or respiratory difficulties such as acute laryngeal edema or bronchial obstruction; * Infants who have used prednisolone or anti-allergic drugs in the past 2 weeks; * Infants with contraindications to eHF or AAF formula; * Infants whose parents are unable to fully report the occurrence of possible symptoms (e.g., insufficient language skills); * Infants with other serious diseases, including but not limited to growth retardation, metabolic disorders, kidney disease, congenital heart disease, medical conditions requiring hospitalization for more than 2 weeks, etc.; * Infants whose mothers are unable to avoid necessary foods when mixed-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Improvement Rate After Elimination Diet Approach (EDA) | 2 weeks after enrolled | The proportion of patients in each group who achieve significant symptom improvement at 2 weeks after starting the diagnostic EDA with different hypoallergenic formulas (amino acid formula \[AAF\] vs. extensively hydrolyzed formula \[eHF\]). Improvement Criteria (must meet at least one of the following for ≥3 consecutive days): * A ≥50% reduction in the Diarrhea and Blood Stool Score (baseline gastrointestinal-dominant symptoms). * A ≥50% reduction in the Cow's Milk-related Symptom Score (CoMiSS) total score. ③ Marked improvement or resolution of original gastrointestinal and/or skin symptoms (e.g., spit-up, vomiting, diarrhea, abdominal distension, abdominal pain, reflux, eczema) as assessed by the attending physician. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieve Significant Symptom Improvement | From enrollment up to 6 weeks (censored at last assessment). | The number of days from the start of the intervention (EDA) until the child first meets the predefined criteria for significant symptom improvement (as defined in the primary outcome). For children who do not achieve improvement within the study period, data will be censored at the last assessment. |
Contacts
CONTACTChundi Xu
CONTACTXinqiong Wang
PRINCIPAL_INVESTIGATORChundi Xu
Ruijin Hospital
Outcome results
None listed