Health of Formula-fed ChildrenLIMENCT02103205
Effect of Infant Formula With Bovine Lactoferrin and Low Iron Concentration on Infant Health and Immune Function
A study testing Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin, Formula with low iron concentration (2mg/L) without lactoferrin and Formula with normal iron concentration (8 mg/L) without lactoferrin in people with Health of Formula-fed Children and Infant Infections in Formula-fed Children, run by Umeå University at 1 site in Sweden.
Trial summary
Breast milk is the gold standard of early infant nutrition and breastfed infants have advantages in several short and long term outcomes compared to those formula-fed. The first aim of this study is to evaluate the effect of adding bovine lactoferrin to infant formula. Read more about this study
- Who is it for?
- Ages 4 to 8 weeksHealthy volunteers can take part
- Conditions the study is for
- Health of Formula-fed Children, Infant Infections in Formula-fed Children, Iron Status of Formula-fed Children
- What is being tested?
- Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin, Formula with low iron concentration (2mg/L) without lactoferrin and Formula with normal iron concentration (8 mg/L) without lactoferrin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 252 participants
- Where
- 1 siteSweden
- Study dates
- Jun 2014to Jan 2025
- 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
- Formula-fed healthy infants at 6 +/- 2 weeks of age with:
- birth weight 2500-4500 g
- gestational age at birth ≥ 37 completed weeks
- no chronic disease or neonatal diagnoses believed to affect any outcome
- no given blood transfusions or iron supplements
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
About this study
Breast milk is the gold standard of early infant nutrition and breastfed infants have advantages in several short and long term outcomes compared to those formula-fed.
The first aim of this study is to evaluate the effect of adding bovine lactoferrin to infant formula. The general hypothesis is that bovine lactoferrin reduces some of the previously observed differences between formula-fed and breast-fed infants with regard to health and development. The main outcome studied is the effect on immune function. The second aim is to study the effects of lower iron concentration in infant formula and to test the hypothesis that iron can be lowered without negative effects on health and development. The main outcome studied here is iron status. Other outcomes in this trial are microbiota composition, metabolomics, growth, body composition and cognitive development.
To test the lactoferrin hypothesis, formula-fed infants will be recruited and fed a low iron (2 mg/L) control formula, or the same formula supplemented with bovine lactoferrin. To test the iron hypothesis, a third group will be fed the same formula (no lactoferrin) with higher iron concentration (8 mg/L). Group allocation for all formula-fed infants will be double-blind randomized. Additionally, breast-fed infants will be recruited and used as a reference group (gold standard).
- Conditions
- Health of Formula-fed Children, Infant Infections in Formula-fed Children, Iron Status of Formula-fed Children
- Being tested
- Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin, Formula with low iron concentration (2mg/L) without lactoferrin, Formula with normal iron concentration (8 mg/L) without lactoferrin
- Keywords
- Lactoferrin, Infant formula, Iron
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrinDietary supplement
Formula with low iron concentration (2mg/L) without lactoferrinDietary supplement
Formula with normal iron concentration (8 mg/L) without lactoferrinDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Low iron, with lactoferrin | Active comparator | Low iron, with lactoferrin Receives: Dietary Supplement: Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin |
| Low iron, no lactoferrin | Active comparator | Low iron, no lactoferrin Receives: Dietary Supplement: Formula with low iron concentration (2mg/L) without lactoferrin |
| Normal iron, no lactoferrin | Placebo comparator | Normal iron, no lactoferrin Receives: Dietary Supplement: Formula with normal iron concentration (8 mg/L) without lactoferrin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of infections
Morbidity journal, Health questionnaire
Measured: Up to 12 months of age
Cytokine levels
IL-2, TNF-alpha
Measured: At 6 months of age
Iron status
s-ferritin, s-transferrin, s-iron, s-transferrin receptor concentration, reticulocyte Hb
Measured: At 6 months of age
Secondary outcomes (14)
Dietary intake
Dietary journal
Measured: At baseline, 3, 4, 5, 6 and 12 months of age
Growth
Anthropometric data, Body Composition (PeaPod)
Measured: At baseline, 4, 6, 12 months of age and 6 years of age
Bloodpressure
Measured: At baseline, 4, 6, 12 months of age and 6 years of age
Antibody response to vaccines
s-levels of specific antibodies to vaccines (DTP, Hib, PC)
Measured: At baseline, 4, 6 and 12 months of age
Gut microbiota
Stool samples
Measured: At baseline, 4, 6, 12 months of age and 6 years of age
Saliva proteins
Saliva total protein content, lactoferrin, saliva-peroxidase, IgA and amylase
Measured: At 4 months of age
Inflammatory markers
s-hsCRP, s-calprotectin
Measured: At baseline, 4, 6 and 12 months of age and 6 years age
Cognitive development and behavior
Bayley III, Wechsler Intelligence Scale for Children (WISC), Behavioral questionnaire
Measured: At 1 and 6 years of age
s-hepcidin
Measured: At baseline, 4, 6, 12 months of age and 6 years of age
Metabolomics
Analyzed in urine and serum samples
Measured: At baseline, 4, 6, 12 months of age and 6 years of age
Amino acids
p-amino acids
Measured: At 4 and 6 months of age
Blood urea nitrogen
p-urea nitrogen
Measured: At 4 and 6 months of age
Cytokine levels
IL-2 and TNF alpha at baseline, 4 and 12 months of age and 6 years of age. Six additional cytokines at baseline, 4, 6 and 12 months of age and 6 years of age.
Measured: At baseline, 4, 6, 12 months of age and 6 years of age
Iron status
s-ferritin, s-transferrin, s-iron, s-transferrin saturation, s-transferrin receptor concentration, retuiculocyte Hb
Measured: At baseline, 4 and 12 months of age and 6 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 posted3 Apr 2014 (estimated)
- Study startJun 2014
- Primary completionMay 2019
- Study completionJan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Health of Formula-fed ChildrenStudies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Mead Johnson Nutrition
- Responsible party
- Principal investigator, Staffan Berglund, Umeå University
- Investigators
- Staffan K Berglund, MD, PhD, Principal investigator, Umeå UniversityOlle Hernell, Professor, Principal investigator, Umeå UniversityBo Lönnerdal, Professor, Principal investigator, University of CaliforniaCarolyn Slupsky, PhD, Principal investigator, University of California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02103205
- Sponsor's protocol ID
- LIME2014
- Acronym
- LIME
- Status last verified
- May 2026
- First submitted
- 31 Mar 2014
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
Bjormsjo M, Hernell O, Lonnerdal B, Berglund SK. Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2022 Mar 1;74(3):e65-e72. doi: 10.1097/MPG.0000000000003367.
PubMed 34908015
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Infant Formula With Bovine Lactoferrin and Low Iron Concentration on Infant Health and Immune Function
- ClinicalTrials.gov ID
- NCT02103205
- Acronym / sponsor ID
- LIME / LIME2014
- Conditions
- Health of Formula-fed Children, Infant Infections in Formula-fed Children, Iron Status of Formula-fed Children
- Keywords
- Lactoferrin, Infant formula, Iron
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Collaborators
- University of California, Mead Johnson Nutrition
- Study start
- Jun 2014
- Primary completion
- May 2019 (actual)
- Study completion
- Jan 2025 (actual)
- First posted
- 3 Apr 2014 (estimated)
- 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.
Breast milk is the gold standard of early infant nutrition and breastfed infants have advantages in several short and long term outcomes compared to those formula-fed.
The first aim of this study is to evaluate the effect of adding bovine lactoferrin to infant formula. The general hypothesis is that bovine lactoferrin reduces some of the previously observed differences between formula-fed and breast-fed infants with regard to health and development. The main outcome studied is the effect on immune function. The second aim is to study the effects of lower iron concentration in infant formula and to test the hypothesis that iron can be lowered without negative effects on health and development. The main outcome studied here is iron status. Other outcomes in this trial are microbiota composition, metabolomics, growth, body composition and cognitive development.
To test the lactoferrin hypothesis, formula-fed infants will be recruited and fed a low iron (2 mg/L) control formula, or the same formula supplemented with bovine lactoferrin. To test the iron hypothesis, a third group will be fed the same formula (no lactoferrin) with higher iron concentration (8 mg/L). Group allocation for all formula-fed infants will be double-blind randomized. Additionally, breast-fed infants will be recruited and used as a reference group (gold standard).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low iron, with lactoferrin | Active comparator | Dietary Supplement: Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrinLow iron, with lactoferrin |
| Low iron, no lactoferrin | Active comparator | Dietary Supplement: Formula with low iron concentration (2mg/L) without lactoferrinLow iron, no lactoferrin |
| Normal iron, no lactoferrin | Placebo comparator | Dietary Supplement: Formula with normal iron concentration (8 mg/L) without lactoferrinNormal iron, no lactoferrin |
Who may qualify
- Ages
- 4 to 8 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- birth weight 2500-4500 g
- gestational age at birth ≥ 37 completed weeks
- no chronic disease or neonatal diagnoses believed to affect any outcome
- no given blood transfusions or iron supplements
Key exclusion criteria (1 listed)
- -
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 |
|---|---|---|
| Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin | Dietary supplement | Low iron, with lactoferrin |
| Formula with low iron concentration (2mg/L) without lactoferrin | Dietary supplement | Low iron, no lactoferrin |
| Formula with normal iron concentration (8 mg/L) without lactoferrin | Dietary supplement | Normal iron, no lactoferrin |
Primary outcome
Incidence of infections
Time frame: Up to 12 months of age
Morbidity journal, Health questionnaire
Cytokine levels
Time frame: At 6 months of age
IL-2, TNF-alpha
Iron status
Time frame: At 6 months of age
s-ferritin, s-transferrin, s-iron, s-transferrin receptor concentration, reticulocyte Hb
14 secondary outcomes
Dietary intake
Time frame: At baseline, 3, 4, 5, 6 and 12 months of age
Growth
Time frame: At baseline, 4, 6, 12 months of age and 6 years of age
Bloodpressure
Time frame: At baseline, 4, 6, 12 months of age and 6 years of age
Antibody response to vaccines
Time frame: At baseline, 4, 6 and 12 months of age
Gut microbiota
Time frame: At baseline, 4, 6, 12 months of age and 6 years of age
Saliva proteins
Time frame: At 4 months of age
Inflammatory markers
Time frame: At baseline, 4, 6 and 12 months of age and 6 years age
Cognitive development and behavior
Time frame: At 1 and 6 years of age
s-hepcidin
Time frame: At baseline, 4, 6, 12 months of age and 6 years of age
Metabolomics
Time frame: At baseline, 4, 6, 12 months of age and 6 years of age
Amino acids
Time frame: At 4 and 6 months of age
Blood urea nitrogen
Time frame: At 4 and 6 months of age
Cytokine levels
Time frame: At baseline, 4, 6, 12 months of age and 6 years of age
Iron status
Time frame: At baseline, 4 and 12 months of age and 6 years of age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Derived from this study: PubMed 34908015Bjormsjo M, Hernell O, Lonnerdal B, Berglund SK. Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2022 Mar 1;74(3):e65-e72. doi: 10.1097/MPG.0000000000003367.
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Infant Growth
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.
Staffan K Berglund, MD, PhD principal investigator
Umeå University
Olle Hernell, Professor principal investigator
Umeå University
Bo Lönnerdal, Professor principal investigator
University of California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin, Formula with low iron concentration (2mg/L) without lactoferrin and Formula with normal iron concentration (8 mg/L) without lactoferrin in people with Health of Formula-fed Children and Infant Infections in Formula-fed Children, run by Umeå University at 1 site 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 5 inclusion and 1 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: finished, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of infections (time frame: Up to 12 months of age). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02103205, which also lists 1 linked publication.
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 28 May 2026.