Cow Milk Protein Allergy, FPIES
Conditions
Brief summary
This study is designed as multicentric, interventional, with two successive randomised, double-blind, crossovers. The aim of the study is to demonstrate the tolerance of an extensively hydrolysed anti-regurgitation casein-based formula in infants with cow's milk protein allergy. After a confirmation of the diagnostic, this demonstration will be performed with oral food challenge. Secondarily, a long term tolerance phase will be performed to get growth outcomes with a consumption of the formula compared with a non-enriched formula.
Interventions
OTHEROral Food Challenge V2
At V2, a randomization is performed and a product is allocated to be administrated in an OFC. According to the randomization the product is EHF-AR or AAF. The progressive doses of 2, 5, 10, 25, 50, and 100 mL are administered to the patient at 15-minute intervals as long as no symptoms appear. If no symptoms appear within 3 hours after administration of the last dose, the product is considered to be tolerated.
OTHERProduct administration between V4 and V5
At V4, a randomization is performed and a product is allocated for the consumption between V4 and V5. According to the randomization, the product is EHF-AR or EHF-STD. The patient will be fed this product for 2 months.
OTHEROral Food Challenge V3
At V3, the second product is administrated (EHF-AR or AAF)(cross-over). The progressive doses of 2, 5, 10, 25, 50, and 100 mL are administered to the patient at 15-minute intervals as long as no symptoms appear. If no symptoms appear within 3 hours after administration of the last dose, the product is considered to be tolerated.
OTHERProduct administration between V5 and V6
At V5, a second allocation is performed and the second product is consumed between V5 and V6 (EHF-AR or EHF-STD)(crossover). The patient will be fed this product for 2 months.
Sponsors
Lactalis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Two successive randomised, double-blind, crossovers
Eligibility
Sex/Gender
ALL
Age
1 Months to 9 Months
Healthy volunteers
No
Inclusion criteria
I1. Age ≥ 1 month and \< 9 months, I2. Exclusively formula fed and planning to be formula-fed for the duration of the study (food diversification allowed), I3. With: 1. a suspicion of CMPA based on suggestive allergic symptoms * CoMISS score \> 10 * And/or acute allergic symptoms * And/or symptoms suggestive of a Food Protein-Induced Enterocolitis Syndrome (FPIES) (major criteria and \<3 minor criteria as per consensus guidelines) (Nowak-Węgrzyn et al. 2017; Beaudoin et al. 2025); OR 2. a confirmed diagnosis of CMPA within the two months before inclusion: * IgE-mediated CMPA (documented history of allergic reaction grade ≤ 3 according to the ordinal food allergy severity score oFASS-5 (Fernández-Rivas et al. 2022) following milk protein ingestion, and sensitization to CMP: blood IgE level specific to cow milk≥ 5 kU/L, or positive skin prick test with papule with fresh cow's milk ≥ 8 mm * or non-IgE-mediated CMPA (documented history of eviction/reintroduction test concluding to CMPA), * or FPIES (major criteria and ≥3 minor criteria as per consensus guidelines (Nowak-Węgrzyn et al. 2017; Beaudoin et al. 2025), I4. With a written informed consent signed by the father and mother or legal representative(s), I5. With parents willing to complete questionnaires, records, and diaries associated to the study and to complete all clinical visits, I6. With parents willing to achieve all study interventions, I7. At least one of the legal representatives is affiliated with a social security scheme.
Exclusion criteria
E1. Birthweight \< 2500 g, E2. Gestational age \< 37 weeks, E3. Breastfeeding at the time of inclusion and throughout the study period, E4. Already fed with an AAF, or with the investigational formula EHF-AR, E5. History of anaphylactic reaction grade 4 or 5 according to classification oFASS-5 (Fernández-Rivas et al. 2022), or of severe FPIES (previous reaction with any change in behaviour from baseline, any pallor and dehydration requiring intravenous fluids), after mammalian milk exposure, E6. Diagnosed or reported fever and/or infectious diseases, or current systemic infections, or history of congenital infections, E7. History / diagnosis of: 1. GI disease or abnormalities (i.e. short bowel syndrome, chronic intestinal diseases, or GI malformations), 2. Or Other malformations, congenital cardiovascular, kidney, liver, pancreas, metabolic or neurological diseases, 3. Or Immunodeficiency, or chronic infection requiring long-term treatment, 4. Or Genetic diseases and chromosomal abnormalities, E8. Suspected or confirmed food allergies or intolerances, other than CMPA, E9. Currently enrolled in another clinical study, or in exclusion period from a previous clinical study, E10. Whose legal representatives have psychological or linguistic incapability to sign the informed consent, E11. Impossibility to contact the legal representatives in case of emergency. After V1, the participant will be excluded from participation in this trial if he/she fulfils the following criteria: E12. No allergic symptoms following the OFC with a standard CMPF.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of infants with CMPA who do not experience any allergic symptoms. | 5 months | The proportion of infants with CMPA who do not experience any allergic symptoms that lead to study discontinuation, as per the investigator, during the first week following the OFC with the EHF-AR formula, including the OFC period itself (between V2 and V3, or V3 and V4). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variation of the CoMISS subscores | 9 months | Variation of the CoMISS subscores (crying, regurgitation, stools, respiratory symptoms, and skin signs) (expressed in arbitrary unit (a.u.), range 0-33) between: * V4 and PC2 * V5 and PC3 * V4 and V5, * V5 and V6. |
| Variation of the IGSQ score | 9 months | Variation of the IGSQ score (expressed in a.u., range 13-65) from V4 to V5, and from V5 to V6. |
| Number of TEAEs | 9 months | * Total number of TEAEs in the allergy body system * Total number of TEAEs in the gastrointestinal body system * Total number of TEAEs |
| Z-scores for age of anthropometric parameters | 9 months | Z-scores for age of anthropometric parameters (length (cm), weight (g) and head circumference (cm)) at V4, V5 and V6 |
| Parents' satisfaction | 9 months | Rate of parents' answer to the following questions: * "Did your baby accept the formula well?" at PC2 and PC3 (yes / somewhat / no), * "Did the formula reduce your baby's spit-up symptoms?" at PC2 and PC3 (yes / somewhat / no / not applicable (no symptoms)), * "Are you generally satisfied with the formula?" at V5 and V6 (yes / somewhat / no), * "Would you recommend this formula to other parents?" at V5 and at V6 (yes / no / no opinion). |
Contacts
CONTACTGrégory ALLAIN
CONTACTBasile FRILLEY
STUDY_DIRECTORGUERVILLE Mathilde
Lactalis
STUDY_DIRECTORCharlotte MAGNANT
Lactalis
PRINCIPAL_INVESTIGATORAnaïs LEMOINE
Hôpital Armand Trousseau - APHP
Outcome results
None listed