Effect of Partially Hydrolyzed Formula With Synbiotics on Skin Barrier Function (SPHINX)

Synbiotics in Partially Hydrolysed Formula for Improved skiN Barrier Function in Infants at Risk for Allergy (SPHINX Study)

The main purpose of this study is to assess the efficacy of a partially hydrolyzed formula with synbiotics in halting one of the first steps of the allergic march (atopic dermatitis) in infants at risk of allergy. Other efficacy and safety parameters will be assessed as well.

Study Overview

• Status: Recruiting
• Conditions: Atopic Dermatitis (AD)
• Intervention / Treatment: Other: Test formula; Other: Control formula

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amelie Goyer, PhD; Phone Number: +41217858939; Email: Amelie.Goyer1@rd.nestle.com

Study Locations

• Belgium
  • Bruges, Belgium
    • Recruiting
    • AZ Sint-Jan Brugge-Oostende AV - Campus Sint-Jan
    • Contact: Luc Cornette, Dr
  • Brussels, Belgium
    • Recruiting
    • Universitair Ziekenhuis Brussel - Kinderziekenhuis
    • Contact: Yvan Vandenplas, Pr
  • Namur, Belgium
    • Recruiting
    • Clinique Ste Elisabeth
    • Contact: Sabine Jespers, Dr
• France
  • Amiens, France
    • Recruiting
    • CHU Amiens Picardie
    • Contact: André Léké, Dr
  • Caen, France
    • Recruiting
    • CHU de Caen
    • Contact: Geraldine Favrais, Pr
  • Grenoble, France
    • Recruiting
    • CHU de Grenoble Alpes
    • Contact: Blandine Rébeillé Borgella
  • Lyon, France
    • Recruiting
    • Hôpital de La Croix Rousse
    • Contact: Jean-Charles Picaud, Pr
  • Rouen, France
    • Recruiting
    • Hopital Charles Nicolle
    • Contact: Mireille Castanet, Dr
  • Tours, France
    • Recruiting
    • Chru De Tours
    • Contact: Kristen Joseph-Delaffon, Dr
• Germany
  • Berlin, Germany
    • Not yet recruiting
    • Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)
    • Contact: Kirsten Beyer, Pr
  • Düsseldorf, Germany
    • Recruiting
    • Evangelisches Krankenhaus Düsseldorf - Frauenklinik
    • Contact: Monika Gappa, Pr
  • Frankfurt, Germany
    • Recruiting
    • Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Frankfurt
    • Contact: Katharina Bluemchen, PD Dr
  • Spandau, Germany
    • Recruiting
    • Evangelisches Waldkrankenhaus Spandau
    • Contact: Frank Jochum, PD Dr
  • Wesel, Germany
    • Not yet recruiting
    • Marien Hospital Wesel GmbH
    • Contact: Cordula Koerner-Rettberg, Dr
• Spain
  • A Coruña, Spain
    • Recruiting
    • Hospital Teresa Herrera
    • Contact: Ana Moreno Álvarez, Dr
  • Almería, Spain
    • Recruiting
    • HU Torrecárdenas
    • Contact: Rafael Galera Martínez, Dr
  • Barcelona, Spain
    • Recruiting
    • Hospital Quiron Salud Barcelona
    • Contact: Hector Boix, Dr
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Severo Ochoa
    • Contact: Maria Luz Garcia, Dr
  • Málaga, Spain
    • Recruiting
    • Grupo Pediatrico Uncibay
    • Contact: Manuel Ramón Baca Cots, Dr
  • Seville, Spain
    • Recruiting
    • Instituto Hispalense de Pediatria (IHP)
    • Contact: Ignacio Salamanca de la Cueva, Dr
  • Tarragona, Spain
    • Recruiting
    • Hospital Universitari Sant Joan de Reus
    • Contact: Joaquín Escribano Subias, Dr
  • Tarragona, Spain
    • Recruiting
    • Hospital Universitari de Tarragona Joan XXIII
    • Contact: Esther Parada Ricart, Dr
  • Zaragoza, Spain
    • Recruiting
    • HCU Lozano Blesa
    • Contact: Gerardo Rodríguez Martínez, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Written informed consent has been obtained from at least one parent or legally acceptable representative (LAR), if applicable
2. Infant gestational age ≥ 37 completed weeks
3. Infant birth weight of ≥ 2.5 kg and ≤ 4.5 kg
4. Infant postnatal age ≤ 14 days (date of birth = day 0) at enrollment
5. Infant from singleton birth or infant from multiple births may if all birth siblings are enrolled.
6. At least one biological parent or sibling has (or had) a medically diagnosed history of allergy, based on response to a simple screening questionnaire

7. a. For the breastfed reference group only: infant is exclusively breastfed since birth with no intake of formula, and their parent(s) have the intention to continue exclusive breastfeeding until at least 4 months of age.

   or b. For the randomized formula-fed groups only: infant is exclusively or predominantly formula-fed in the 24 hours prior to enrollment, with formula feeding representing at least 75% of total daily feeds. The decision to introduce formula feeding was independently made by the parents before enrollment.

8. Parents/LAR must be able to provide evidence of parental authority and identity.
9. Infant's parent(s)/LAR must understand the informed consent form and other study documents and are willing and able to fulfill the requirements of the study protocol.

Exclusion Criteria:

1. Infectious, metabolic, congenital, genetic, gastrointestinal illness or any other condition (e.g., gastrointestinal surgery) that could impact oral feeding, growth or study outcomes.
2. Infants with special dietary needs other than standard infant formula (e.g., extensively hydrolyzed formula, amino acid formula, special formula for metabolic diseases) or requiring tube feeding.
3. Infant has already been diagnosed with allergy by a physician, including AD and/or cow's milk allergy.
4. Infant is currently participating or has previously participated in another clinical trial prior to enrollment.
5. Infant's parents or LARs have not reached legal age of majority (18 years).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test formula; Partially hydrolyzed formula with synbiotics	Other: Test formula; Partially hydrolyzed formula with synbiotics
Active Comparator: Control formula; Intact protein formula without synbiotics	Other: Control formula; Intact protein formula without synbiotics
No Intervention: Reference arm; Breastfed arm (not applicable for France)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TransEpidermal Water Loss (TEWL) at 3 months	TransEpidermal water loss will be measured using a validated non-invasive technique.	At 3 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of Atopic Dermatitis	Cumulative incidence of AD is based on physician diagnosis using the United Kingdom Working Party (UKWP) diagnosis criteria.	From enrollment to 12 months of age
TransEpidermal Water Loss	Epidermal water loss will be measured using a validated non-invasive technique.	From enrollment to 12 months of age
Skin surface (stratum corneum) hydration	Skin hydration will be measured with a corneometer device.	From enrollment to 12 months of age
Extent and severity of Atopic Dermatitis	SCORAD (SCORing for Atopic Dermatitis), scores range from 0 to 103, with higher scores indicating higher atopic dermatitis severity	From 3 months to 12 months of age
Cumulative use of topical steroids and calcineurin inhibitors	Use of medication to treat AD and other symptoms will be collected via parent self-reported questionnaire.	From enrollment to 12 months of age
Skin cytokines	Concentration of skin cytokines such as IL4 and IL5 using immunoassays	From enrollment to 12 months of age
Skin natural moisturizing factors	Concentration of skin natural moisturizing factors such as Pyrrolidone carboxylic acid, using HPLC	From enrollment to 12 months of age
Skin stratum corneum lipids	Concentration of skin stratum corneum lipids such as ceramides, cholesterol and triacylglycerol using mass spectrometry	From enrollment to 12 months of age
Skin microbiome	Overall skin microbiome composition and diversity using next-generation sequencing	From enrollment to 12 months of age
Skin metabolites	Levels of skin metabolites using targeted or untargeted approaches.	From enrollment to 12 months of age
Immune proteomics	Levels of plasma proteins using mass cytometry or immunoassaysand immunoassays.	From enrollment to 6 months of age
Immune blood cell immunophenotyping	Levels of immune cell populations using mass cytometry or immunoassays	From enrollment to 6 months of age
Specific IgE antibodies	Specific IgE antibodies will be measured using Phadiatop infant®.	At 12 months of age
Fecal microbiome	Overall fecal microbiota composition, diversity, different bacteria taxa and microbiota community types assessed using next generation sequencing (NGS) technology	From enrollment to 12 months of age
Fecal metabolites	Levels of fecal metabolites using targeted or untargeted approaches.	From enrollment to 12 months of age
Fecal biomarkers of inflammation and immunity	Levels of fecal markers of immune health and inflammation such as total secretory IgA (sIgA), calprotectin, and α-1-antitrypsin assessed by ELISA.	From enrollment to 12 months of age
Physician-diagnosed allergic manifestations	Number of participants with Physician-diagnosed allergic manifestations.	From enrollment to 12 months of age
Gastrointestinal tolerance	Infant Gastrointestinal Symptom Questionnaire (IGSQ), scores range from 13 to 65, with higher scores indicating higher gastrointestinal discomfort.	At enrollment and 4 months of age
Weight	Weight (g and z-scores)	From enrollment to 12 months of age
Height	Length (cm and z-scores)	From enrollment to 12 months of age
Head circumference	Head circumference (cm and z-scores)	From enrollment to 12 months of age
Safety assessment	Incidence of adverse events	From enrollment to 13 months of age

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic
• Other Study ID Numbers: 2215INF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No