Clinical trial NCT06130085: Partially Hydrolyzed Formula in Cow's Milk Protein Allergy After 6 Months of Elimination
Official title: Open Labeled Randomized Clinical Trial of Introduction of a Partially Hydrolyzed Formula in Cow's Milk Protein Allergy After 6 Months of Elimination Protocol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cow's Milk Protein Allergy
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2023-11-13
Enrollment: 100
Sex: ALL
Minimum age (years): 7
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: For Patients diagnosed as cow milk protein allergy: Elimination of cow's milk products (CMPs) for 6 months.

All infants were supplemented with Amino Acid-based Formula (AAF) (Neocate infant®/ Neocate junior®, Dannone Nutricia) for 6 months at start of elimination diet.

For mixed milk fed infants (still receiving breast milk with the formula), mothers were encouraged to continue breast-feeding while avoiding all milk and milk products from their own diet.

Intervention after completing 6 months of eliminating CMPs. The included patients were randomly assigned to one of (2 groups).

1. Group I (AAF group) n= 50 Infants in this group continued with Amino Acid-based Formula for another 6 months.
2. Group II (pHF group) n= 50 Infants in this group were shifted gradually to Partially-hydrolyzed whey formula (pHF) (Liptomil Plus HA infant formula. for another 6 months with continuation of elimination of cow's milk products.

They were followed up for manifestations of intolerance to pHF. Infant who showed manifestations of intolerance were returned to AAF and continued for 6 months with AAF.

Final step: Reintoduction of CMPs After 12 months of elimination of CMPs, evaluation of tolerance to whole CMPs was done by oral food challenge (OFC).

For infants who were still non-tolerant to CMPs after 12 months of elimination were followed up and re-challenged after 6 months.

Detailed description: Phase Ⅰ:Initial assessment at enrollment i. Full medical history taking: with emphasis on: Personal History: Age- Sex- Order of birth- Consanguinity-Residence

Main presenting symptoms:

A- Gastrointestinal symptoms: at initial diagnosis According to the clinical presentations, following clinical diagnoses were identified GERD, FPIAP, FPIES, FPE, constipation and combination of symptoms as shown in the following table.

B- Associated systemic allergic manifestations: at initial diagnosis C- CoMiSS: Cow's Milk-related Symptom Score (CoMiSS) at presentation. CMPA diagnosis was confirmed by an elimination diet followed by an oral food challenge.

D- Course of the disease:

E- Dietary and nutritional history:

1. Breast Feeding: If Yes exclusive for how long?
2. Artificial feeding: Age of start, type of formula, Indication.
3. Weaning: Time of start, Type of food given (each food and time of introduction especially cow's milk and CMPs), Any problems during weaning (gastrointestinal, respiratory or skin allergies) and eliciting dose of milk products that caused symptoms.
4. Accidental intake of raw or heated milk during elimination period and its consequences.

   * Past history: mode of delivery
   * Family history: atopy, siblings with CMPA
   * Medication history: Antireflux medications, laxatives, probiotics. ii. Clinical examination:
   * Anthropometric measurements: (weight \&height on Z score, Wt/Ht ratio) using WHO 2006 Growth charts to those aged ≤ 2 years \& CDC Growth charts 2000 if \>2 years old
   * Signs of allergy: (atopic dermatitis- allergic rhinitis-wheezy chest)
   * Abdomen:(Distension- Tenderness- organomegaly)
   * Perineal area: (Perianal inflammation, napkin rash)

Phase 2: Elimination of CMPs for 6 months. All infants were supplemented with Amino Acid-based Formula (Neocate infant®/ Neocate junior®, Dannone Nutricia) for 6 months at start of elimination diet. Cow's-milk-based formula and supplementary foods containing CMPs, other animal milk proteins (eg, goat's milk, sheep's milk) were strictly avoided due to cross reactivity.

For mixed milk fed infants (still receiving breast milk with the formula), mothers were encouraged to continue breast-feeding while avoiding all milk and milk products from their own diet Breast feeding mothers excluding cow's milk were prescribed a supplement of 1000 mg of calcium \& 10 µg (400 IU) of vitamin D every day

Phase III: Intervention after completing 6 months of eliminating CMPs

o The included patients were randomly assigned to one of (2 groups).

1. Group I (AAF group) n= 50 Infants in this group continued with Amino Acid-based Formula for another 6 months.
2. Group II (pHF group) n= 50 Infants in this group were shifted gradually the same way as OFC (from Amino Acid-based Formula; to Partially-hydrolyzed whey formula (Liptomil Plus HA infant formula; for another 6 months with continuation of elimination of CMPs.

They were followed up for manifestations of intolerance to pHF. Infant who showed manifestations of intolerance were returned to AAF and continued for 6 months with AAF.

Phase IV: Reintroduction of CMPs After 12 months of elimination of CMPs, evaluation of tolerance to whole CMPs was done by OFC. Tolerance was established by a negative challenge followed by regular ingestion of age-appropriate quantities of cow's milk at home without symptoms, where patients were followed up again for one month to detect any symptoms of intolerance after regular ingestion of milk products

For infants who were still non-tolerant to CMPs after 12 months of elimination were followed up and re-challenged after 6 months.

Eligibility criteria: Inclusion Criteria:

1. Artificially fed infants whether exclusively or complementary.
2. Confirmed diagnosis of CMPA based on clinical symptoms and signs and followed by withdrawal open re-challenge test

Exclusion Criteria:

1. Exclusively breast-fed infants.
2. Anaphylactic type.
3. Multiple food Allergies.

Primary outcomes:
measure: compare the rate of tolerance to cow milk products among patients allocated to partially hydrolyzed formula after 6 months of milk free diet compared to those who completed 1 year of elimination
timeFrame: At the month 13 for both groups and for extra more 30 days of regular ingestion of cow's milk products
Secondary outcomes:
measure: Tolerance to pHF after 6 months elimination diet
timeFrame: At the seventh month in the group allocated to receive pHF after six months of elimination diet
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University
Study officials:
References:
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