Infant FormulaGRANDIOSANCT05578716
Growth, Allergy and Neurodevelopment in Infants on Hydrolysed Formula
A study testing Partially hydrolysed formula in people with Infant Formula, run by Umeå University at 2 sites in Sweden.
Trial summary
Breastfeeding is the recommended diet for all infants during the first half of infancy and is associated with numerous health benefits. However, when breastfeeding is not possible, an infant formula is the only nutritive alternative. Formula-fed infants have a different growth pattern compared to breastfed infants. Read more about this study
- Who is it for?
- Ages 4 to 8 weeksHealthy volunteers can take part
- Conditions the study is for
- Infant Formula
- What is being tested?
- Partially hydrolysed formula
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 312 participants
- Where
- 2 sitesSweden
- Study dates
- 3 Oct 2022to Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 8 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy infants born at term
- Birth weight 2500 to 4500 gram
- Either exclusive breast-feeding (reference group) or exclusive formula-feeding (intervention and control group)
Who cannot join
- Suspected or verified food allergy
- Suspected or verified infant colic
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites, 2 recruiting
- Recruiting
Department of clinical science, Preventive Paediatrics, Lund university
Malmö, 20502
Pia Karlsland-Akeson, MD, PhD, pia.karlsland_akeson@med.lu.se
Pia Karlsland-Akeson, MD, PhD
- Recruiting
Department of Clinical Sciences, Pediatrics, Umeå University Hospital
Umeå, 901 85
Magnus Domellöf, MD, PhD, 0046 90 7852128, magnus.domellof@umu.se
Magnus Domellöf, MD, PhD
About this study
Official title: GRANDIOSA - Growth, Allergy and Neurodevelopment in Infants on Hydrolysed Formula
Breastfeeding is the recommended diet for all infants during the first half of infancy and is associated with numerous health benefits. However, when breastfeeding is not possible, an infant formula is the only nutritive alternative. Formula-fed infants have a different growth pattern compared to breastfed infants. Studies have shown that the higher protein content in infant formula compared to breastmilk results in a more rapid weight gain and an increased risk of overweight and obesity in childhood. For this reason, both quantity and quality of protein in infant formulae have been optimized during the last decade, to better meet the needs of infants and to support growth close to that of breastfed infants.
Protein hydrolysis, a common modification of infant formulae, has originally been developed for treatment of cow's milk protein allergy. Certain hydrolysed formulae have been suggested to prevent atopic eczema when given to infants with a family history of allergic disease but as of yet, the allergy preventive effect in infants without increased risk of allergic disease has been little studied. Partially hydrolysed infant formulae have also been suggested to reduce common functional gastrointestinal symptoms in infants.
Read more
New protein hydrolysates are continually developed for use in infant formulae, with the aim of reducing allergenicity, while ensuring optimal growth and development of infants. It is important to study the effects on growth and health outcomes in infants who are fed formulae based on these newly developed hydrolysates as compared to those fed standard intact protein formulae or breastmilk.
The overall aims of the current study are to evaluate the effects of two new hydrolysates on growth, immunological biomarkers, neurodevelopment, protein metabolism and gut microbiota in a randomized, controlled clinical trial of healthy infants. In compliance with European Food Safety Authority (EFSA) regulations for novel infant formulas based on hydrolysed protein, the primary outcome is change in weight standard deviation score (SDS) from baseline until 5 months of age.
- Conditions
- Infant Formula
- Being tested
- Partially hydrolysed formula
- Keywords
- Infant nutrition, Food hypersensitivity, Dermatitis, Atopic, Protein hydrolysates, Spectroscopy, Near-Infrared
- Medical subject headings
- Food Hypersensitivity, Dermatitis, Atopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Partially hydrolysed formulaDietary supplement
Partially hydrolysed formula
| Study group | Role | What they receive |
|---|---|---|
| Study formula 1 | Experimental | Formula-fed intervention group randomised to one of two study formulae Receives: Dietary Supplement: Partially hydrolysed formula |
| Study formula 2 | Experimental | Formula-fed intervention group randomised to one of two study formulae Receives: Dietary Supplement: Partially hydrolysed formula |
| Standard formula | No intervention | Formula-fed control group randomised to standard formula |
| Breast feeding | No intervention | Reference group with exclusively breast-fed infants |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight
Primary outcome is weight Standard Deviation Score (SDS) at the end of the intervention.
Measured: At 5 months of age
Secondary outcomes (15)
Length.
Growth pattern during the course of the intervention measured by length in centimeters and SDS.
Measured: At enrollment at 2 months of age and monthly during the intervention up to 5 months of age.
Head circumference.
Growth pattern during the course of the intervention measured by head circumference in centimeters and SDS.
Measured: At enrollment at 2 months of age and monthly during the intervention up to 5 months of age.
Body composition
Assessing differences in body composition between study groups using fat percentage as measured by PeaPod (Pletysmography).
Measured: At 4 months of age
Gastrointestinal tolerance.
Gastrointestinal tolerance using diary for information about stool frequency and consistency (in four grades from diarrhea to hard stools) in combination with questionnaire filled in by the parents based on Rome IV criteria for functional gastrointestinal disorders.
Measured: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Gastrointestinal immunology.
Markers of gastrointestinal immune activation using analysis of calprotectin, eosinophilic derived neurotoxin and secretory Immunoglobulin A (IgA) in fecal samples.
Measured: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Eczema severity, parent report.
Parents will fill in the Patient-Oriented Eczema Measure (POEM) score monthly during the intervention.
Measured: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Eczema severity, clinical assessment.
Excema severity is assessed at every study visit using the Eczema Area and Severity Index (EASI).
Measured: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Allergy.
Sensitization to cow's milk protein is assessed by Immunoglobulin E (IgE) in serum using ImmunoCap.
Measured: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Immunologic activity.
Blood cytokine patterns using Luminex: Interleukin 2 (IL-2) as a marker of general T cell activity. Interferon gamma (IFN-γ) as a marker of Helper T cells type 1 (Th1) activity. Interleukin 4 (IL-4) as a marker of helper T cells type 2 (Th2) activity. Tumor growth factor beta type 1 (TGF-β1) as a marker of T cell regulatory activity. Interleukin 17 A (IL17-A) as a marker of helper T cell type 17 (Th17) activity. C reactive protein (CRP) in plasma as a marker of general inflammatory response.
Measured: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Metabolic biomarkers in blood.
Insulin-like growth factor-1 (IGF-1). Insulin. C-peptide. Leptin. Leptin-receptor.
Measured: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Markers of protein metabolism.
Plasma amino acids. Blood urea nitrogen.
Measured: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Microbiota
Composition and diversity of the gut microbiota analysed in fecal samples. Bacterial DNA will be extracted and the V3-V4 region of the 16S rRNA gene will be amplified. Sequencing of all samples takes place on the Illumina MiSeq platform. Based on the results, we will also use metagenomic or Nanopore sequencing for deeper characterization of microbial composition and functions.
Measured: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Neurodevelopment at 6 months of age.
Response in cerebral blood flow to visual and auditory stimuli as measured by functional near-infrared spectroscopy (fNIRS).
Measured: At 6 months of age.
Neurodevelopment at 12 months of age.
Bayely scales of infant development (BSID) 3rd edition. Higher score is interpreted as better outcome.
Measured: At 12 months of age.
Neurodevelopment at 3 years of age.
Wechsler Preschool and Primary Scale of Intelligence (WIPPSI) 4th edition. Higher score is interpreted as better outcome.
Measured: At 3 years of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start3 Oct 2022
- Primary completionJun 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infant FormulaStudies of the same condition, open and under way.
- More trials run by Umeå UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised to either standard formula or one of two partially hydrolysed study formulae. Included in the study will also be a group of breast-fed infants acting as reference group.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 312 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University, Arla Foods
- Responsible party
- Principal investigator, Magnus Domellöf, Umeå University
- Investigators
- Magnus Domellöf, MD, PhD, Principal investigator, Department of Clinical Sciences, Pediatrics, Umeå University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05578716
- Sponsor's protocol ID
- 20210707401
- Acronym
- GRANDIOSA
- Status last verified
- Dec 2023
- First submitted
- 19 Sep 2022
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRANDIOSA - Growth, Allergy and Neurodevelopment in Infants on Hydrolysed Formula
- ClinicalTrials.gov ID
- NCT05578716
- Acronym / sponsor ID
- GRANDIOSA / 20210707401
- Conditions
- Infant Formula
- Keywords
- Infant nutrition, Food hypersensitivity, Dermatitis, Atopic, Protein hydrolysates, Spectroscopy, Near-Infrared
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 312 participants (estimated)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Collaborators
- Lund University, Arla Foods
- Study start
- 3 Oct 2022 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 13 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Breastfeeding is the recommended diet for all infants during the first half of infancy and is associated with numerous health benefits. However, when breastfeeding is not possible, an infant formula is the only nutritive alternative. Formula-fed infants have a different growth pattern compared to breastfed infants. Studies have shown that the higher protein content in infant formula compared to breastmilk results in a more rapid weight gain and an increased risk of overweight and obesity in childhood. For this reason, both quantity and quality of protein in infant formulae have been optimized during the last decade, to better meet the needs of infants and to support growth close to that of breastfed infants.
Protein hydrolysis, a common modification of infant formulae, has originally been developed for treatment of cow's milk protein allergy. Certain hydrolysed formulae have been suggested to prevent atopic eczema when given to infants with a family history of allergic disease but as of yet, the allergy preventive effect in infants without increased risk of allergic disease has been little studied. Partially hydrolysed infant formulae have also been suggested to reduce common functional gastrointestinal symptoms in infants.
New protein hydrolysates are continually developed for use in infant formulae, with the aim of reducing allergenicity, while ensuring optimal growth and development of infants. It is important to study the effects on growth and health outcomes in infants who are fed formulae based on these newly developed hydrolysates as compared to those fed standard intact protein formulae or breastmilk.
The overall aims of the current study are to evaluate the effects of two new hydrolysates on growth, immunological biomarkers, neurodevelopment, protein metabolism and gut microbiota in a randomized, controlled clinical trial of healthy infants. In compliance with European Food Safety Authority (EFSA) regulations for novel infant formulas based on hydrolysed protein, the primary outcome is change in weight standard deviation score (SDS) from baseline until 5 months of age.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Participants will be randomised to either standard formula or one of two partially hydrolysed study formulae. Included in the study will also be a group of breast-fed infants acting as reference group.
| Arm | Type | Receives |
|---|---|---|
| Study formula 1 | Experimental | Dietary Supplement: Partially hydrolysed formulaFormula-fed intervention group randomised to one of two study formulae |
| Study formula 2 | Experimental | Dietary Supplement: Partially hydrolysed formulaFormula-fed intervention group randomised to one of two study formulae |
| Standard formula | No intervention | –Formula-fed control group randomised to standard formula |
| Breast feeding | No intervention | –Reference group with exclusively breast-fed infants |
Who may qualify
- Ages
- 4 to 8 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Healthy infants born at term
- Birth weight 2500 to 4500 gram
- Either exclusive breast-feeding (reference group) or exclusive formula-feeding (intervention and control group)
Key exclusion criteria (2 listed)
- Suspected or verified food allergy
- Suspected or verified infant colic
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Partially hydrolysed formulaPartially hydrolysed formula | Dietary supplement | Study formula 1, Study formula 2 |
Primary outcome
Weight
Time frame: At 5 months of age
Primary outcome is weight Standard Deviation Score (SDS) at the end of the intervention.
15 secondary outcomes
Length.
Time frame: At enrollment at 2 months of age and monthly during the intervention up to 5 months of age.
Head circumference.
Time frame: At enrollment at 2 months of age and monthly during the intervention up to 5 months of age.
Body composition
Time frame: At 4 months of age
Gastrointestinal tolerance.
Time frame: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Gastrointestinal immunology.
Time frame: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Eczema severity, parent report.
Time frame: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Eczema severity, clinical assessment.
Time frame: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Allergy.
Time frame: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Immunologic activity.
Time frame: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Metabolic biomarkers in blood.
Time frame: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Markers of protein metabolism.
Time frame: At enrollment at 2 months of age and at the end of the intervention at 5 months of age.
Microbiota
Time frame: At enrollment at 2 months of age and during the intervention up to 5 months of age.
Neurodevelopment at 6 months of age.
Time frame: At 6 months of age.
Neurodevelopment at 12 months of age.
Time frame: At 12 months of age.
Neurodevelopment at 3 years of age.
Time frame: At 3 years of age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Magnus Domellöf, MD, PhD principal investigator
Department of Clinical Sciences, Pediatrics, Umeå University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Partially hydrolysed formula in people with Infant Formula, run by Umeå University at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Magnus Domellöf, MD, PhD (+46907852128, magnus.domellof@umu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight (time frame: At 5 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.