TITLE: A Randomized Control Trial of a Supervised Peanut Feeding Clinic to Increase Early
Peanut Introduction A. Specific Aims/Objectives We aim to assess if a supervised peanut
feeding clinic within a general pediatrics practice can increase early peanut
introduction and peanut feeding frequency by caregivers in their infants. We hypothesize
that parents in the intervention arm who are offered a supervised peanut feeding clinic
for their child's first feeding will be feeding peanuts more regularly at home than
parents in the control arm who receive only standard guidance.
B. Background and Significance.1 in 13 children are allergic to at least one food, many are allergic to two or more,
with significant associated mortality, morbidity, and economic costs1. In particular,
peanut allergy is the leading pediatric food allergy in the United States, affecting
~2.5% of children2. Furthermore, approximately 83% of adults with peanut allergy report
childhood onset, showing that children with peanut allergies are largely not outgrowing
or being cured of this allergy3. While there are several treatments either available or
in trials for curing or at least managing peanut allergy, they are expensive, time
intensive, and thus not widely available4. Until recently we have had no way to prevent
the onset of peanut allergy.
In 2015 the LEAP study showed that early and frequent consumption of peanut products
starting by age 7 months in high-risk infants was protective against the development of a
peanut allergy in childhood, with an 80% reduction in peanut allergy in those in the
intervention group compared to controls who followed standard feeding guidelines at the
time5. Infant feeding guidelines were changed in 2017 to recommend early peanut
introduction for high-risk infants. Subsequent research has shown the benefits of early
peanut introduction in all infants prompting a guideline change again in 2020 to promote
early peanut introductions for all infants6,7.
Despite the robust research, the theoretical ease of implementation, and the benefits to
individuals and society of guideline adherence, we continue to see low buy-in from
parents. A study published in Pediatrics in 2023 by Samady and colleagues8 assessed 3062
caregivers of children ages 7 months to 3.5 years in 2021 regarding their peanut
introduction habits. They stratified results by those who were aware of the guidelines;
and, even amongst guideline aware parents, only 31% offered peanuts prior to 7-months
with another 19.7% offering peanuts between 7-8 months. Among guideline aware parents,
8.4% offered peanuts daily or almost daily and 34.5% offered peanuts a few times a week.
Finally, among guideline aware parents, reasons given for why they waited until after 7
months or did not feed at all were fear of an allergic reaction, being unaware of how to
feed peanuts to an infant, and a disbelief in the guidelines.
This research shows us that while there is work to be done to ensure pediatricians are
providing the guidelines to parents, guideline knowledge alone will not get us to the
levels of peanut consumption in infancy that we need to make a true difference in peanut
allergy prevalence. One intervention proposed in the 2017 guidelines is a supervised
feeding clinic in the general pediatrician's office9
- - this would address parents' fear
of an allergic reaction as well as help alleviate their concerns about how to feed
peanuts to an infant.
However, to our knowledge no study has systematically looked at the
effectiveness of offering a supervised feeding clinic. This study will look at the effect
of a dedicated supervised feeding clinic on the outcome of increasing peanut introduction
and consumption frequency through a randomized control trial.
C. Preliminary Studies To the best of our knowledge, there is no prior research to date
specifically looking at the impact of a structured supervised peanut feeding clinic
within a general pediatrics clinic setting on the rate of early peanut introduction and
peanut feeding frequency in infancy.
D. Design and Methods. 1. Study Design This will be an unblinded randomized control trial with two groups
(Figure 1). It is not possible to blind either participants or the research team as
only one group will be offered the supervised feeding clinic visit. Study team
members will contact families by phone in the week after their 4-month well child
visit to discuss the study and screen for eligibility. Initial information will
briefly detail the goals of the study (to assess ways to help caregivers provide
peanuts to their infants) and will alert them to the possibility of being assigned
to the group with an extra visit, which will be billed to their insurance as a
regular pediatric follow up. Caregivers who remain interested in the study will then
be provided an e-consent form to enroll. All participants will receive a standard
guideline handout on peanut introduction to eliminate any bias from what different
pediatricians might have time to discuss with their patients and isolate the effect
of the supervised feeding clinic in guideline aware caregivers. This handout is a
standard guideline packet created by the Asthma and Allergy Foundation of America
that is available for public use and used in our primary care clinic. Participants
will then be randomized. Randomization will occur using a pre-generated block
randomization chart
- - the chart will be twice as long as expected enrollment.
The
randomization determines who is offered this new resource of a supervised feeding
visit, no participant is required to attend this additional visit.
As we anticipate some caregivers will decline to participate in the study, and their
reasons for doing so may inform the feasibility of offering such a clinic in the
future, we will offer exit interviews for people who decline to enroll
- - we
anticipate there might be concerns regarding transportation or visit copays related
to this additional visit that we will want to assess.
Families who do not wish to
enroll in the RCT will be offered an opportunity to enroll in a brief qualitative
interview study, anticipated to take 5 minutes, to discuss any reasons they may have
had for not wanting to join the study.
2. Patient Selection and Inclusion/Exclusion Criteria All children after their 4-month
well child check at our three clinical practices located at Children's Hospital
Primary Care Center, Martha Eliot Health Center, and Weymouth will be assessed for
eligibility. Exclusion criteria include: 1) infants who are not developmentally able
to eat solids prior to age 7 months, 2) families who do not speak English, or 3)
infants who have already eaten peanuts, have a positive peanut IgE (note they do not
need to have a negative peanut IgE
- - a blood test to look for evidence of an allergy
- in order to be enrolled in the study but some providers may have gotten one in
their usual practice and inadvertently found a positive result), or there are other
concerns regarding an existing allergy to peanuts.
For any peanut allergy concerns
families should be evaluated by their pediatrician and referred to Allergy &
Immunology.
Participants in the intervention arm must be at baseline state of health on the day
of the supervised feeding visit, but they may be re-scheduled to another date.
Unlike an oral food challenge in an Allergist's office for a known or suspected food
allergy, participants in this intervention arm may have used antihistamines in the
days prior to the visit. This is because this is not considered an oral food
challenge, and we do not give families any such restrictions before feeding peanuts
for the first time at home.
3. Description of Study Treatments or Exposures/Predictors The intervention arm will be
invited to a supervised feeding clinic visit. At this clinic visit, which will take
place prior to age 7 months, infants will be fed peanut butter (provided by the
study team) mixed into a vehicle of choice brought by the caregivers (e.g. yogurt,
cereal, mashed fruit, etc). For infants whose parents forget to bring in a mixing
vehicle, we will provide apple sauce or water for thinning out the peanut butter.
Feeding peanut butter itself is a minimal risk study exposure as we ask all families
to do this at home by themselves without any medications or clinical team available.
For this study, we are offering half the group to do what we normally ask them to do
at home in the presence of a clinical team. No one in the intervention arm is
required to come for this additional supervised peanut feeding visit.
4. Definition of Primary and Secondary Outcomes/Endpoints Our primary outcome is the
percentage of families who have introduced peanuts by age 9 months within the home
diet. Secondary outcomes include a weekly average of how often they are feeding
peanut products and an average quantity fed per feeding. We will also include a
balancing measure to assess if attendance at later well child visits (e.g. 9-month
well child visit) is impacted by coming in for an additional visit earlier on.
5. Data Collection Methods, Assessments, Interventions and Schedule (what assessments
performed, how often) All participants will receive a baseline survey after study
enrollment. All participants will receive a second survey at age 9 months. Surveys
were adapted from the survey used in Samady et al.8 Those in the intervention arm
will be offered an in person visit to feed peanut butter to their infant in a
monitored clinical setting. This visit will take place prior to age 7 months.
6. Study Timeline (as applicable) We anticipate beginning study enrollment in May 2025
and continuing through October 2025 with later enrolled participants finishing study
activities in January 2026. We plan to analyze our data from January to February
2026.
E. Adverse Event Criteria and Reporting Procedures This is a minimal risk study and the
study exposure
- - feeding peanut products to infants - is the same exposure we ask parents
to do at home on their own already without medical supervision or allergic reaction
treatments available.
There is no new drug or supplement being investigated in this
study. The only anticipated adverse event is an allergic reaction, which we expect to
happen as rarely as it may occur at home (approximately <1% of the time and usually a
small rash). All allergic reactions during supervised feeding visits will be documented
within the clinical visit and appropriate treatment for the allergic reaction will be
administered.
F. Data Management Methods All data will be stored in REDCap. G. Quality Control Method.To ensure the reliability, consistency, and safety of the study, the following quality
control procedures will be implemented throughout the duration of the randomized
controlled trial:
1. Randomization Process The randomization process will involve a pre-made block
randomization chart which will be used for the study duration. Randomization will
occur prior to any study activities.
2. Intervention Consistency. • Clinic Visits: The intervention group will be offered a structured clinic visit,
during which the baby will be examined, fed peanut butter, and then monitored for an
allergic reaction. Each clinic visit will be standardized to ensure consistency in
the process.
- - Standardized Feeding Protocol: ZA will administer the peanut butter with the
family according to a standardized protocol.
The protocol will include specific
instructions on the amount of peanut butter to be given, how to safely
introduce it to the baby, and any necessary monitoring for adverse reactions.
- - Supervision: The intervention will be completed by ZAwho is a pediatrician who
will monitor the baby for signs of allergic reaction during the feeding and for
30 minutes afterward.
Any signs of distress will be immediately addressed in
accordance with the clinic's emergency procedures.
- - Documentation: Each clinic visit will be documented, including the amount of
peanut butter given, any adverse reactions, and participant feedback.
These
records will be reviewed. 3. Staff Training Only the co-investigator, Zara Rafi Atal, will be running the clinic
intervention visits. She has received training through her general pediatrics
practice in the correct administration of peanut butter to ensure safe feeding
practices, recognition and management of allergic reactions (e.g., anaphylaxis,
hives), and standardized procedures for documentation.
4. Data collection and Monitoring.
- - Data Collection Tools: Standardized forms will be used for recording baseline
data, clinic visit details, and follow-up data.
- - Adverse Events Monitoring: Any adverse events related to the peanut butter
feeding (e.g. allergic reactions) will be documented.
5. Protocol Deviations and Corrective Actions In the event of a protocol deviation
(e.g., incorrect administration of peanut butter or missed clinical visits), these
will be documented, and corrective actions will be implemented. A detailed log will
track all deviations and the steps taken to rectify them. The study steam will
review these deviations regularly to identify trends and improve future practices.
6. Participant Feedback and Safety Checks Participants will be provided with clear
instructions on what to do in case of an allergic reaction (e.g., contacting the
clinic or visiting the emergency room), ensuring they have appropriate support if
needed.
H. Data Analysis Plan For our primary aim we will treat our outcome as a dichotomous
variable (0 = no introduction to peanuts by 9 months; 1=introduction to peanuts by 9
months). For our secondary aim we will treat our outcome as a dichotomous variable (0 =
feeding peanuts 2 or fewer times a week and 1 = feeding peanuts 3 or more times per
week). Our primary analysis will be an intention to treat analysis based on initial
randomization group. We will run two-sample test of proportions to look at the proportion
of caregivers who report at the 9-month visit that they have introduced peanuts to their
infants in the intervention versus control group as well as the proportion of caregivers
who report at the 9-month visit that they are giving their infant peanuts 3 or more times
per week in the intervention versus control group.
Multivariable logistic regression will be used for the per-protocol analysis (comparing
those who attend the supervised feeding visit to the control group) to adjust for
variables that will be unbalanced once the analysis is limited to the per-protocol group.
- I. Statistical Power and Sample Considerations Power calculations were done using SAS.
With a sample of 58 subjects per group, we will have 80% power to detect a 50% difference
in the group proportions (0.5 to 0.75) of peanut introduction prior to 9-months using a
two-sided two-sample test of proportions with a significance level of 0.05. With a sample
size of 80 subjects per group (of those who do introduce peanuts) we will have 80% power
to detect a 50% difference in the group proportions (0.4 to 0.6) of frequency of peanut
provided prior to 9-months using a two-sided two-sample test of proportions with a
significance level of 0.05. To be able to test our second aim of peanut frequency and
assuming a conservative 50% peanut introduction rate by the 9-month visit we will aim to
enroll 160 per group. To account for a 25% loss to follow up we will aim to enroll in
total 200 participants per group. Across the 3 clinics we see approximately 30 4-month
well child checks per week or about 120 per month.
