HealthyNCT00994747
Sensitive Periods in Early Flavor Learning
A study testing Nutramigen (Flavor and Type of Infant Formula) and Enfamil, milk-based formula in people with Healthy, run by Monell Chemical Senses Center at 1 site in United States.
Trial summary
Flavor is the primary dimension by which young children determine food acceptance. However, children are not merely miniature adults since sensory systems mature postnatally and their responses to certain tastes differ markedly from adults. Read more about this study
- Who is it for?
- Ages 2 to 4 weeksHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Nutramigen (Flavor and Type of Infant Formula) and Enfamil, milk-based formula
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Jun 2010
- 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 2 to 4 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy, term infants of any racial background
- Infants may be of either sex
- Infants must be 2 weeks of age
- Infants must be exclusively feeding a cow's milk-based formula
- Mothers must be over 18 years of age
Who cannot join
- Infants who were preterm
- Infants who have medical conditions that interfere with feeding or eating
- No major complications during pregnancy or at birth
Trial locations and contacts
1 site in 1 country.
United States1 site
Monell Chemical Senses Center
Philadelphia, Pennsylvania, 19104
About this study
Flavor is the primary dimension by which young children determine food acceptance. However, children are not merely miniature adults since sensory systems mature postnatally and their responses to certain tastes differ markedly from adults. Moreover, emerging research has revealed that there are sensitive periods during infancy such that early flavor experiences serve to modify later responses to flavors and foods. The proposed study aims to investigate this important issue by using as a model system a class of infant formulas which are hydrolyzed protein based and thus have very pronounced and distinctive flavors which are unpalatable to older-aged infants and adults. This research was initiated because of anecdotal reports by pediatricians that although it is easy to introduce this type of formula to infants during the first months of life, it becomes extremely difficult to do so later in infancy. Indeed, recent studies in the investigators' laboratory provided the first experimental demonstration that infants younger than 4 months of age willingly accept substantial amounts of, and satiate while feeding, a novel, protein hydrolysate formula. In marked contrast, infants older than 4 months reject the protein hydrolysate formula and this rejection occurs within the first minute of a feed, a finding that strongly suggests the sensory qualities of the formula are responsible, at least in part, for this rejection. Moreover, this rejection is not evident when the investigators test older-aged infants with other unfamiliar, but non-hydrolysate, formulas. In other words, the rejection appears to be in response to a particular component or components of protein hydrolysate formulas. This shift in acceptability can be ameliorated by prior exposure. That is, if these formulas are introduced to infants within the first few months of life and are fed continuously, they remain highly acceptable throughout infancy and early childhood. These observations implicate a sensitive period during development, occurring somewhere before 4 months of age, during which exposure to a formula, which is unpalatable to adults and infants over 4 months of age without exposure, renders it acceptable and presumably palatable. To the investigators' knowledge, this is the clearest example of a sensitive period in the development of responses to foods and flavors in humans thus far identified.
There is a paucity of information on whether and how the composition of formulas fed to infants influences their short-term feeding behaviors during the first few months of life. The primary objective of this longitudinal study is to determine the period during early infancy when exposure to the casein-hydrolysate formula, Nutramigen, renders it acceptable during later infancy. The study also aims to determine how early sensory experiences with formula impact upon food acceptance during infancy (8-9 months of age) and childhood. The investigators will also explore how variation in the genes that encode for taste receptors influence preferences for foods and other behaviors.
Read the detailed description
This is a basic research, longitudinal and experimental study in which infants will be randomized into one of six groups (N=10-15 per group) differing in the timing and type of formula that the infant will be fed during each month of the 7-month exposure period. Each mother-infant dyad will be studied from the 2-3rd week of life until approximately 9 months of age. When the infant is less than three weeks of age and the mother's decision to formula feed is well established, infants will be randomized into one of six groups differing in the timing and type of formula that the infant will be fed during each month of the 7-month exposure period. One group (Control EEEEEEE) will be assigned to a milk-based formula, Enfamil (E), whereas another group (NNNNNNN) will be assigned to Nutramigen (N) during the entire 7-month period of this study. The other 4 groups will be assigned to feed Nutramigen for specified periods during their first seven months of life (Groups ENEEEEE, EEENEEE, ENNNEEE).
A variety of methodologies developed in our laboratory will be employed to capture the infants' responses to a particular flavor or taste after the exposure period. That is, at the end of the exposure period, infants will be videotaped while they are 1) feeding formulas; 2) feeding foods (e.g., cereal; soups) that differ in flavors; and 3) exploring scented toys. Each month, infants will be weighed and measured for length as well as evaluated for cognitive and motor development and mothers will completed standardized questionnaires regarding infant temperament. A cheek swab from the mothers and infants will be obtained and genotyped for taste receptor and taste- and obesity- related genes.
- Conditions
- Healthy
- Being tested
- Nutramigen (Flavor and Type of Infant Formula), Enfamil, milk-based formula
- Keywords
- infancy, nutrition, protein hydrolysate formula, flavor preferences, food preferences, growth, emotional development, mother-infant interaction, infant temperament, feeding patterning, taste receptor and obesity genotype, sensitive period
- Medical subject headings
- Food Preferences
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nutramigen (Flavor and Type of Infant Formula)Other
Nutramigen, protein hydrolysate formula, fed to infants as sole formula source during specified times during the first 8.5 months of life
Enfamil, milk-based formulaOther
Enfamil, milk-based formula, fed as formula source during first 8.5 months of life
| Study group | Role | What they receive |
|---|---|---|
| Group EEEEEEE | Active comparator | Infant is fed Enfamil from 0.5-7.5 months of life Receives: Other: Enfamil, milk-based formula |
| Group ENEEEEE | Experimental | Infant is fed Enfamil during 0.5-1.5 months of life, Nutramigen from 1.5-2.5 months of life and then Enfamil 2.5-7.5 of life. Receives: Other: Nutramigen (Flavor and Type of Infant Formula) |
| Group EENEEEE | Experimental | Infant is fed Enfamil 0.5-2.5 months of life, Nutramigen from 2.5-3.5 months of life and then Enfamil from 3.5 to 7.5 months of life Receives: Other: Nutramigen (Flavor and Type of Infant Formula) |
| Group EEENEEE | Experimental | Infant is fed Enfamil from 0.5-3.5 months of life, Nutramigen from 3.5-4.5 months of life and then Enfamil from 4.5-7.5 months of life. Receives: Other: Nutramigen (Flavor and Type of Infant Formula) |
| Group ENNNEEE | Experimental | Infant if fed Enfamil from month 0.5-1.5 months of life, Nutramigen from 1.5 to 3.5 months of life and then Enfamil again 3.5-7.5 months of life. Receives: Other: Nutramigen (Flavor and Type of Infant Formula) |
| Group NNNNNNN | Experimental | Infant is fed Nutramigen from 0.5-7.5 months of life. Receives: Other: Nutramigen (Flavor and Type of Infant Formula) |
What is being measured
The primary outcome is the main question the study is designed to answer.
infants' intake, length of feeding and patterning of feeding of Nutramigen relative to Enfamil (infant-led feeding condition)
Measured: 0.5-8.5 months
Secondary outcomes (6)
infant growth (weight and length)
Measured: 0.5 to 8.5 months of life
maternal perceptions of infant enjoyment of feeding
Measured: 8.5 months
infants' exploration of toys as a function of scent
Measured: 9 months
infants' intake of foods as a function of flavor and chemical composition
Measured: 8 months and 2-3 years
infants' temperament and behavioral development
Measured: 0.5 months -2years
taste receptor and obesity genotypes.
Measured: 8 months and 2-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2009 (estimated)
- Study startNov 2006
- Primary completionMay 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monell Chemical Senses Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Julie A. Mennella, Monell Chemical Senses Center
- Investigators
- Julie A Mennella, PhD, Principal investigator, Monell Chemical Senses Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00994747
- Sponsor's protocol ID
- 803712
- Status last verified
- Oct 2012
- First submitted
- 12 Oct 2009
- Last updated
- 3 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Mennella JA, Lukasewycz LD, Castor SM, Beauchamp GK. The timing and duration of a sensitive period in human flavor learning: a randomized trial. Am J Clin Nutr. 2011 May;93(5):1019-24. doi: 10.3945/ajcn.110.003541. Epub 2011 Feb 10.
PubMed 21310829Mennella JA, Ventura AK, Beauchamp GK. Differential growth patterns among healthy infants fed protein hydrolysate or cow-milk formulas. Pediatrics. 2011 Jan;127(1):110-8. doi: 10.1542/peds.2010-1675. Epub 2010 Dec 27.
PubMed 21187303Mennella JA, Trabulsi JC, Papas MA. Effects of cow milk versus extensive protein hydrolysate formulas on infant cognitive development. Amino Acids. 2016 Mar;48(3):697-705. doi: 10.1007/s00726-015-2118-7. Epub 2015 Oct 26.
PubMed 26497857
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sensitive Periods in Early Flavor Learning
- ClinicalTrials.gov ID
- NCT00994747
- Acronym / sponsor ID
- 803712
- Conditions
- Healthy
- Keywords
- infancy, nutrition, protein hydrolysate formula, flavor preferences, food preferences, growth, emotional development, mother-infant interaction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Monell Chemical Senses CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Nov 2006
- Primary completion
- May 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 14 Oct 2009 (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.
Flavor is the primary dimension by which young children determine food acceptance. However, children are not merely miniature adults since sensory systems mature postnatally and their responses to certain tastes differ markedly from adults. Moreover, emerging research has revealed that there are sensitive periods during infancy such that early flavor experiences serve to modify later responses to flavors and foods. The proposed study aims to investigate this important issue by using as a model system a class of infant formulas which are hydrolyzed protein based and thus have very pronounced and distinctive flavors which are unpalatable to older-aged infants and adults. This research was initiated because of anecdotal reports by pediatricians that although it is easy to introduce this type of formula to infants during the first months of life, it becomes extremely difficult to do so later in infancy. Indeed, recent studies in the investigators' laboratory provided the first experimental demonstration that infants younger than 4 months of age willingly accept substantial amounts of, and satiate while feeding, a novel, protein hydrolysate formula. In marked contrast, infants older than 4 months reject the protein hydrolysate formula and this rejection occurs within the first minute of a feed, a finding that strongly suggests the sensory qualities of the formula are responsible, at least in part, for this rejection. Moreover, this rejection is not evident when the investigators test older-aged infants with other unfamiliar, but non-hydrolysate, formulas. In other words, the rejection appears to be in response to a particular component or components of protein hydrolysate formulas. This shift in acceptability can be ameliorated by prior exposure. That is, if these formulas are introduced to infants within the first few months of life and are fed continuously, they remain highly acceptable throughout infancy and early childhood. These observations implicate a sensitive period during development, occurring somewhere before 4 months of age, during which exposure to a formula, which is unpalatable to adults and infants over 4 months of age without exposure, renders it acceptable and presumably palatable. To the investigators' knowledge, this is the clearest example of a sensitive period in the development of responses to foods and flavors in humans thus far identified.
There is a paucity of information on whether and how the composition of formulas fed to infants influences their short-term feeding behaviors during the first few months of life. The primary objective of this longitudinal study is to determine the period during early infancy when exposure to the casein-hydrolysate formula, Nutramigen, renders it acceptable during later infancy. The study also aims to determine how early sensory experiences with formula impact upon food acceptance during infancy (8-9 months of age) and childhood. The investigators will also explore how variation in the genes that encode for taste receptors influence preferences for foods and other behaviors.
Detailed description
This is a basic research, longitudinal and experimental study in which infants will be randomized into one of six groups (N=10-15 per group) differing in the timing and type of formula that the infant will be fed during each month of the 7-month exposure period. Each mother-infant dyad will be studied from the 2-3rd week of life until approximately 9 months of age. When the infant is less than three weeks of age and the mother's decision to formula feed is well established, infants will be randomized into one of six groups differing in the timing and type of formula that the infant will be fed during each month of the 7-month exposure period. One group (Control EEEEEEE) will be assigned to a milk-based formula, Enfamil (E), whereas another group (NNNNNNN) will be assigned to Nutramigen (N) during the entire 7-month period of this study. The other 4 groups will be assigned to feed Nutramigen for specified periods during their first seven months of life (Groups ENEEEEE, EEENEEE, ENNNEEE).
A variety of methodologies developed in our laboratory will be employed to capture the infants' responses to a particular flavor or taste after the exposure period. That is, at the end of the exposure period, infants will be videotaped while they are 1) feeding formulas; 2) feeding foods (e.g., cereal; soups) that differ in flavors; and 3) exploring scented toys. Each month, infants will be weighed and measured for length as well as evaluated for cognitive and motor development and mothers will completed standardized questionnaires regarding infant temperament. A cheek swab from the mothers and infants will be obtained and genotyped for taste receptor and taste- and obesity- related genes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group EEEEEEE | Active comparator | Other: Enfamil, milk-based formulaInfant is fed Enfamil from 0.5-7.5 months of life |
| Group ENEEEEE | Experimental | Other: Nutramigen (Flavor and Type of Infant Formula)Infant is fed Enfamil during 0.5-1.5 months of life, Nutramigen from 1.5-2.5 months of life and then Enfamil 2.5-7.5 of life. |
| Group EENEEEE | Experimental | Other: Nutramigen (Flavor and Type of Infant Formula)Infant is fed Enfamil 0.5-2.5 months of life, Nutramigen from 2.5-3.5 months of life and then Enfamil from 3.5 to 7.5 months of life |
| Group EEENEEE | Experimental | Other: Nutramigen (Flavor and Type of Infant Formula)Infant is fed Enfamil from 0.5-3.5 months of life, Nutramigen from 3.5-4.5 months of life and then Enfamil from 4.5-7.5 months of life. |
| Group ENNNEEE | Experimental | Other: Nutramigen (Flavor and Type of Infant Formula)Infant if fed Enfamil from month 0.5-1.5 months of life, Nutramigen from 1.5 to 3.5 months of life and then Enfamil again 3.5-7.5 months of life. |
| Group NNNNNNN | Experimental | Other: Nutramigen (Flavor and Type of Infant Formula)Infant is fed Nutramigen from 0.5-7.5 months of life. |
Who may qualify
- Ages
- 2 to 4 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Healthy, term infants of any racial background
- Infants may be of either sex
- Infants must be 2 weeks of age
- Infants must be exclusively feeding a cow's milk-based formula
- Mothers must be over 18 years of age
Key exclusion criteria (3 listed)
- Infants who were preterm
- Infants who have medical conditions that interfere with feeding or eating
- No major complications during pregnancy or at birth
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 |
|---|---|---|
| Nutramigen (Flavor and Type of Infant Formula)Nutramigen, protein hydrolysate formula, fed to infants as sole formula source during specified times during the first 8.5 months of life | Other | Group EEENEEE, Group EENEEEE, Group ENEEEEE, Group ENNNEEE, Group NNNNNNN |
| Enfamil, milk-based formulaEnfamil, milk-based formula, fed as formula source during first 8.5 months of life | Other | Group EEEEEEE |
Primary outcome
infants' intake, length of feeding and patterning of feeding of Nutramigen relative to Enfamil (infant-led feeding condition)
Time frame: 0.5-8.5 months
6 secondary outcomes
infant growth (weight and length)
Time frame: 0.5 to 8.5 months of life
maternal perceptions of infant enjoyment of feeding
Time frame: 8.5 months
infants' exploration of toys as a function of scent
Time frame: 9 months
infants' intake of foods as a function of flavor and chemical composition
Time frame: 8 months and 2-3 years
infants' temperament and behavioral development
Time frame: 0.5 months -2years
taste receptor and obesity genotypes.
Time frame: 8 months and 2-3 years
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 3 Oct 2012.
- Results publication: PubMed 21310829Mennella JA, Lukasewycz LD, Castor SM, Beauchamp GK. The timing and duration of a sensitive period in human flavor learning: a randomized trial. Am J Clin Nutr. 2011 May;93(5):1019-24. doi: 10.3945/ajcn.110.003541. Epub 2011 Feb 10.
- Results publication: PubMed 21187303Mennella JA, Ventura AK, Beauchamp GK. Differential growth patterns among healthy infants fed protein hydrolysate or cow-milk formulas. Pediatrics. 2011 Jan;127(1):110-8. doi: 10.1542/peds.2010-1675. Epub 2010 Dec 27.
- Derived from this study: PubMed 26497857Mennella JA, Trabulsi JC, Papas MA. Effects of cow milk versus extensive protein hydrolysate formulas on infant cognitive development. Amino Acids. 2016 Mar;48(3):697-705. doi: 10.1007/s00726-015-2118-7. Epub 2015 Oct 26.
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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.
Julie A Mennella, PhD principal investigator
Monell Chemical Senses Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nutramigen (Flavor and Type of Infant Formula) and Enfamil, milk-based formula in people with Healthy, run by Monell Chemical Senses Center at 1 site in United States.
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 3 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 3 Oct 2012. 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 United States. 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?
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?
infants' intake, length of feeding and patterning of feeding of Nutramigen relative to Enfamil (infant-led feeding condition) (time frame: 0.5-8.5 months). 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 NCT00994747, which also lists 3 linked publications.
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 3 Oct 2012.