Neonatal Esophagus and Airway Interactions in Health and Disease
Phase: NA
Conditions: Dysphagia, Airway Aspiration, Airway Penetration
Sponsor: Sudarshan Jadcherla

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
Page 1 of 17 
HRP-503  v.12.10.18 
 
PROTOCOL TITLE: 
Neonatal Esophagus and Airway Interactions in Health and Disease: Mechanisms and 
Management of Infant Dysphagia  
 
PRINCIPAL INVESTIGATOR: 
Name: Sudarshan Jadcherla 
Department/Center: Neonatal and Infant Feeding Disorders Program/Center for 
Perinatal Research 
Telephone Number: (614) 355-6643 
Email Address: Sudarshan.Jadcherla@nationwidechildrens.org 
VERSION NUMBER/DATE: 
Version 10(revision #9) 10/2/20 
REVISION HISTORY 
 
Revision 
# 
Version 
Date 
Summary of Changes 
Consent 
Change? 
1 
12/21/15 During the intervention phase while thickened formula is 
in use, we changed the definition of compliance from < 
or equal to 75% of the time to < or equal to 50% of the 
time 
No 
2 
1/12/16 
Allowed less percentage of PO intake at time of 
screening to account for provider led restrictions vs. 
infant led restrictions 
No 
3 
2/26/16 
1. Allowed subjects on acid suppressive therapies at 
the time of VFSS into our recruitment as well as 
allow oatmeal as a second option for thickening. 
2. Added the addition of video use during 
manometry in our methods section. Concurrent 
synchronized video recordings will be performed 
to further validate symptoms based on objective 
definition of the esophageal reflexes. 
Documentation of symptom markers can be 
validated by integrating manometry with 
respiratory inductance plethysmography and 
video. 
3. Updates to the PHI page and privacy section of 
the consent to state the infant's face will be in 
view of the video. 
4. Updated DSMB members. 
Yes  
4 
4/24/17 
Changed reimbursement language to reflect use of 
ClinCard 
Yes 

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
5 
6/12/17 
At inception, the protocol was written as a randomized 
control trial comparing two different feeding approaches: 
flow regulation vs. thickened feeds. However, over the 
period, we found it difficult to recruit and retain subjects. 
Based on the recommendations of the DSMB and 
program project team, we addressed the hypotheses using 
alternative strategies. One of such strategies is reflected 
in this amendment, wherein, the proposed change instead 
of the interventions being randomly assigned, parents 
will now choose which therapeutic feeding strategy they 
would like to enroll their infant in. This is called the 
parent-preferred feeding therapeutic strategy. 
Yes 
6 
10/18/17 Replaced redlined version of protocol with clean version 
Yes 
7 
2/8/18 
A detailed review of the protocol as written revealed 
multiple changes in study team members and data 
collection methods that had not been addressed in the 
body of the protocol. Although the focus and outcome 
measures of the study have not changed, the protocol was 
amended to reflect the updates suggested by the DSMB. 
Yes 
8 
1/4/19 
Updates to statistical analysis and sample size as well as 
updated protocol to new template 
Yes for new 
IRB 
requirements 
9 
10/2/20 
Clarification and summary of changes to the protocol 
thus far have been made for improved readability, 
reproducibility and clarity for the reader as this needs to 
be submitted along with the manuscript. 
No 
 
 
1.0 
Study Summary 
 
Study Title 
Neonatal Esophagus and Airway Interactions in Health and Disease: 
Mechanisms and Management of Infant Dysphagia  
Study Design 
Single arm observational study 
Primary 
Objective 
Our overall aims are to identify novel diagnostic aerodigestive targets, 
define effective therapeutic interventions, and advance the mechanistic 
basis of therapeutic outcomes-i.e., full oral feedings. 
Secondary 
Objective(s) 
1) Examine the differences in outcomes among preterm born vs. full 
term born 
2) Examine the differences in outcomes among those with normal 
versus abnormal VFSS 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Providing esophageal manometry concurrent with video fluoroscopy 
swallow study (VFSS) in order to determine sensory-motor dysphagic 
mechanisms which will better inform treatment options 
IND/IDE #  
N/A 

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
Study 
Population 
All infants will have a diagnostic VFSS scheduled. 
 
Inclusions: Infants with feeding-related aerodigestive symptoms who are < 
60 weeks PMA (both pre-term and full-term) who are orally feeding > 25% 
of at least 50% of their feeds who are on full enteral feeds with no more 
than 1LPM NC respiratory support.   
 
Exclusions: Genetic or metabolic syndromes, IVH grade III or greater, 
moderate to severe HIE, craniofacial, airway or foregut malformations or 
ENT or neuro surgeries. Infants who are exclusively breastfeeding are also 
excluded.  
 
Sample Size 
60 
Study Duration 
for individual 
participants 
Up to 4 weeks (initial manometry study with diagnostic VFSS, repeat 
manometry at 4-6 weeks as relevant), will follow feeding outcomes and 
growth and developmental outcomes for 1 year 
Study Specific 
Abbreviations/ 
Definitions  
VFSS video-fluoroscopy swallow study 
LP laryngeal penetration 
LA laryngeal aspiration 
 
2.0 
Objectives 
2.1 
Purpose, Specific Aims or Objectives 
• Our overall aims are to identify novel diagnostic 
aerodigestive targets, define effective therapeutic 
interventions, and advance the mechanistic basis of 
therapeutic outcomes. Infants with aerodigestive and 
feeding difficulties, who had VFSS undergo Manometry 
study to ascertain the mechanisms of normal or abnormal 
swallowing. Parent-preferred therapy is implemented. 
Changes in therapy modes are documented. Repeat 
manometry study is undertaken at time-2, which is 2-4 
weeks after the initial study where feasible (this may 
happen in those with oral feeding failures).   
• Based on the VFSS results evaluations, there are 2 possible 
scenarios: those with abnormal or normal results. Parent 
preferred therapeutic feeding (flow change, thickener 
change, no change) strategy is implemented and we will 
simply monitor the progress of the feeding efficiency till 
discharge or four weeks, whichever is earlier. There are 2 
possible outcomes: feeding success, i.e., full oral feeds 
without symptom requiring intervention or feeding failure, 
i.e., those needing any tube feeding.  
• We will review the motility characteristics of the successful 
and failure cases to identify the diagnostic markers.  

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
2.2 
Hypothesis 
• The central unifying hypothesis supported by our 
preliminary data is that VFSS with the addition of 
Manometry along with parent preferred feeding strategy is 
more effective in preventing long term feeding tubes in 
infants with aerodigestive problems and feeding 
difficulties.  
• Primary Hypothesis: The addition of manometry for 
diagnostics and parent preferred therapy for management is 
more effective than VFSS with provider recommendations 
alone for achieving primary outcome.  
• Secondary Hypotheses: 1) The sensory- motor 
characteristics of pharyngo-esophageal motility markers are 
distinctive between normal and abnormal VFSS results. 2) 
Clinical outcomes are distinct with flow modification and 
thickener use.  
3.0 
.Background 
3.1 
Relevant prior experience and gaps in current knowledge.  
• Dysphagia or abnormalities of swallowing, is a 
heterogeneous condition of multiple etiologies. Pharyngeal 
phase is the most critical phase since imprecise regulation 
is associated with airway consequences such as laryngeal 
penetration and airway aspiration. Exact prevalence is not 
known, but is estimated to be about 30% to 60% among 
neonatal ICU graduates. Although these numbers highlight 
the economic burden, they ignore the quality of life for 
both patients and parents. The lack of a pathophysiology 
guided diagnostic and safe feeding management strategies 
continue to be critical barriers to progress in this field. The 
current proposal focuses on the dynamic changes in the 
integrative physiology of the neonatal pharynx, upper 
esophageal sphincter (UES), lower esophageal sphincter 
(LES) and esophagus during swallowing and GERD; all of 
which are potential therapeutic targets for neonates with 
dysphagia. Current treatment approaches in dysphagic 
infants are likely to fail due to unclear therapeutic targets. 
Such high risk infants also suffer chronic morbidity, longer 
hospitalizations, re-admissions, and account for an 
unacceptable health care burden. Designing effective 
symptom-based management is very difficult. 
3.2 Relevant preliminary data.  

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
• Three references are attached below in this section that lend 
support to our investigations, difficulties with strict 
protocols and need for personalization and parent preferred 
pragmatic therapies. Complimentary protocols (feeding 
outcomes in dysphagia, mechanisms of dysphagia, 
outcomes in gastrostomy bound infants) will address the 
original study aims as well. Updated statistical procedures 
based on the advice of our statistician, Dr. Lai Wei, PhD, 
DSMB team, and our Program Project Group is shown 
below.  
3.3 
Updated statistical procedures: 
• The design of the Patient Preferred Trial has been modified 
to a single arm observational study with patients who have 
not achieved PO at the time of study or PO with feeding 
difficulties, comparing VFSS and manometry vs VFSS 
only (the historical control) on feeding outcomes. The 
primary outcome is success rate at discharge. We will 
prospectively follow 60 infants who are not fully PO or PO 
and symptomatic at the time of study. Based on our 
Feeding Outcomes of Dysphagia Study (vs. historical 
control), the success rate at discharge is around 60%.  With 
60 patients enrolled, we will have 90% power to detect an 
absolute increase of 20% from 60% for those who do not 
have treatment informed by manometry (historical control) 
to 80% in those in the manometry informed group with 
two-sided type I error of 0.05. Achievement will be 
assessed by tracking feeding methods at discharge or 4 
weeks whichever is earlier and then at 1 year.  
• Jadcherla SR, Peng J, Moore R, Saavedra J, Shepherd E, 
Fernandez S, Erdman SH, DiLorenzo C. Impact of 
personalized feeding program in 100 NICU infants: 
pathophysiology-based approach for better outcomes. J 
Pediatr Gastroenterol Nutr. 2012 Jan;54(1):62-70.   
• Jadcherla SR, Stoner E, Gupta A, Bates DG, Fernandez S, 
Di Lorenzo C, Linscheid T. Evaluation and management of 
neonatal dysphagia: impact of pharyngoesophageal motility 
studies and multidisciplinary feeding strategy. J Pediatr 
Gastroenterol Nutr. 2009 Feb;48(2):186-92  
• Jadcherla SR, Khot T, Moore R, Malkar M, Gulati IK, 
Slaughter JL. Feeding Methods at Discharge Predict Long-
Term Feeding and Neurodevelopmental Outcomes in 
Preterm Infants Referred for Gastrostomy Evaluation. J 
Pediatr. 2017 Feb;181:125-130   

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
3.4 
Scientific or scholarly background for, rationale for, and 
significance of the research based on the existing literature and how 
will it add to existing knowledge 
• This proposal is a logical extension of our current P01 and 
is built on Novel Concepts, and State-Of-The-Art Methods 
[1-14,15-20], and the field will be changed if the proposed 
aims are achieved: In the previous funding period, we 
characterized the reciprocal physiology between the 
esophagus and aerodigestive tract in premature infants.  
The studies indicated airway protective reflexes undergo 
maturation through the early stages of life and their absence 
or aberrance is associated with dysphagia and its 
complications. We will extend this knowledge to test 
diagnostic yield as well as novel feeding management 
strategies for dysphagia.  
• The central unifying hypothesis supported by our 
preliminary data is that VFSS with the addition of 
Manometry along with parent preferred feeding strategy is 
more effective in preventing long term feeding tubes in 
infants with aerodigestive problems and feeding 
difficulties.  
• We will investigate the sensory-motor mechanisms relevant 
to dysphagic infants. Dysphagia may be attributed to 
luminal clearance mechanisms and failure of airway 
protective mechanisms: esophageal mechano-distention and 
chemo-sensitive stimulation induced aerodigestive reflexes. 
The mechanisms for symptoms may lie in stimulus 
thresholds, response-frequency, response-latency and 
response-magnitude of the aerodigestive protective 
reflexes. In those with persistent failure, a time 2 study is 
undertaken where feasible to ascertain dysfunctional 
mechanisms. Unique to this proposal, we will apply 
physiologically rational, safe, therapeutic strategies that 
have the potential to ameliorate dysphagia We anticipate 
finding that feeding methods underlie the pathogenesis of 
dysphagia and reveal relevant new therapeutic targets. 
• Publications History and References Pertinent to this 
Proposal are as follows:   
o Jadcherla SR, Hasenstab KA, Shaker R, Castile RG. 
Mechanisms of cough provocation and cough 
resolution in neonates with bronchopulmonary 
dysplasia. Pediatr Res. 2015 Oct;78(4):462-9. doi: 
10.1038/pr.2015.131. Epub 2015 Jul 7. PubMed 

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
PMID: 26151491; PubMed Central PMCID: 
PMC4800483 
o Babaei A, Venu M, Naini SR, Gonzaga J, Lang IM, 
Massey BT, Jadcherla S, Shaker R. Impaired upper 
esophageal sphincter reflexes in patients with 
supraesophageal reflux disease. Gastroenterology. 
2015 Nov;149(6):1381-91. doi: 
10.1053/j.gastro.2015.07.007. PubMed Central 
PMCID: PMC4628603 
o Jadcherla SR, Shubert TR, Malkar MB, Sitaram S, 
Moore RK, Wei L, Fernandez S, Castile RG. 
Gestational and postnatal modulation of esophageal 
sphincter reflexes in human premature neonates. 
Pediatr Res. 2015 Nov;78(5):540-6. doi: 
10.1038/pr.2015.149. PubMed PMID: 26270576; 
PubMed Central PMCID: PMC4628557 
o Madhoun LL, Siler-Wurst KK, Sitaram S, Jadcherla 
SR. Feed-Thickening Practices in NICUs in the 
Current Era: Variability in Prescription and 
Implementation Patterns. J Neonatal Nurs. 2015 
Dec 1;21(6):255-262. PubMed PMID: 26664251; 
PubMed Central PMCID: PMC4671396. (PO1 DK 
068051, R01 DK 068158) 
o Jadcherla SR. Dysphagia in the high-risk infant: 
potential factors and mechanisms. Am J Clin Nutr. 
2016 Feb;103(2):622S-8S. doi: 
10.3945/ajcn.115.110106. Review. PubMed PMID: 
26791178; PubMed Central PMCID: PMC4733255 
o Jadcherla SR, Hasenstab KA, Sitaram S, Clouse BJ, 
Slaughter JL, Shaker R. Effect of nasal noninvasive 
respiratory support methods on pharyngeal 
provocation-induced aerodigestive reflexes in 
infants. Am J Physiol Gastrointest Liver Physiol. 
2016 Jun 1;310(11):G1006-14. doi: 
10.1152/ajpgi.00307.2015. PubMed PMID: 
27012774; PubMed Central PMCID: PMC4935482. 
(PO1 DK 068051) 
o Lang IM, Medda BK, Jadcherla SR, Shaker R. 
Characterization and mechanisms of the pharyngeal 
swallow activated by stimulation of the esophagus. 
Am J Physiol Gastrointest Liver Physiol. 2016 Nov 
1;311(5):G827-G837. doi: 

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
Disease: Mechanisms and Management of Infant Dysphagia 
 
 
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HRP-503  v.12.10.18 
10.1152/ajpgi.00291.2016. PubMed PMID: 
27634013; PubMed Central PMCID: PMC5130554. 
o  Jadcherla SR. Advances with Neonatal 
Aerodigestive Science in the Pursuit of Safe 
Swallowing in Infants: Invited Review. Dysphagia. 
2017 Feb;32(1):15-26. doi: 10.1007/s00455-016-
9773-z. Review. PubMed PMID: 28044203; 
PubMed Central PMCID: PMC5303645. 
o Mei L, Jiao H, Sharma T, Dua A, Sanvanson P, 
Jadcherla SR, Shaker R. Comparative effect of the 
sites of anterior cervical pressure on the geometry 
of the upper esophageal sphincter high-pressure 
zone. Laryngoscope. 2017 Nov; 127(11): 2466-
2474. doi: 10.1002/lary.26642. Epub 2017 May 23. 
PubMed PMID: 28543926. (PO1 DK 068051, R01 
DK 025731, T32 DK 061923) 
o Hasenstab KA, Sitaram S, Lang IM, Shaker R, 
Jadcherla SR. Maturation Modulates Pharyngeal-
Stimulus Provoked Pharyngeal and Respiratory 
Rhythms in Human Infants. Dysphagia. 2018 Feb; 
33(1): 63-75. doi: 10.1007/s00455-017-9833-z. 
Epub 2017 Aug 21.  PubMed PMID: 28828751 
o Lang IM, Medda BK, Shaker R, Jadcherla SR.  The 
effect of body position on esophageal reflexes in 
cats: A possible mechanism of SIDS? Pediatr Res. 
2017 Dec 20. doi: 10.1038/pr.2017.302. [Epub 
ahead of print] PubMed PMID:  29166377.  
o Jadcherla SR, Prabhakar V, Hasenstab KA, Nawaz 
S, Das J, Kern M, Balasubramanian G, Shaker R. 
Defining pharyngeal contractile integral during 
high-resolution manometry in neonates: a 
neuromotor marker of pharyngeal vigor. Pediatr 
Res. 2018 Jul 6. doi: 10.1038/s41390-018-0097-6. 
[Epub ahead of print] PMID: 29976974 
o Levy DS, Osborn E, Hasenstab KA, Nawaz S, 
Jadcherla SR. The Effect of Additives for Reflux or 
Dysphagia Management on Osmolality in Ready-to-
Feed Preterm Formula: Practice Implications. JPEN 
J Parenter Enteral Nutr. 2018 Jul 10. doi: 
10.1002/jpen.1418. [Epub ahead of print] PMID: 
29992586 
 

PROTOCOL TITLE: Neonatal Esophagus and Airway Interactions in Health and 
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4.0 
Study Endpoints 
4.1 The study endpoint will be independent oral feeding without 
symptoms requiring intervention by 4 weeks or sooner. 
4.2 The study will be ended with any safety concerns for the subject 
5.0 
Study Intervention/Investigational Agent 
5.1 The intervention will be the addition of either concurrent or 
sequential high resolution esophageal manometry with the VFSS as 
well as a follow up esophageal manometry as needed. This is an 
accepted diagnostic tool used in infants with feeding difficulties. 
6.0 
Procedures Involved* 
6.1 
Study Design  
• Study design and setting: Eligible subjects (study) will 
undergo diagnostic VFSS in combination with manometry, 
either concurrent or sequential. They will have parental 
choice of preferred feeding therapy. The data is from single 
center prospective observational study. The controls are 
those who had VFSS alone with provider recommendations 
from the same single center.  
• Patient population and characteristics: (i) Study and control 
infants have oral feeding difficulties with symptoms 
requiring interventions/monitoring. (ii) They have 
diagnostic need for VFSS due to aerodigestive and feeding 
difficulties. (iii) Study subjects must have a signed 
informed consent from parent/legal guardian prior to 
manometry study.  Control subjects did not require consent 
as they were historical controls. 
• Inclusion criteria: Infants with feeding-related 
aerodigestive symptoms who are < 60 wks PMA (both pre-
term and full-term) who are orally feeding > 25% of at least 
50% of their feeds who are on full enteral feeds with no 
more than 1LPM NC respiratory support. All infants will 
have a diagnostic VFSS scheduled.  
• Exclusion criteria: Genetic or metabolic syndromes, grade 
III or greater, moderate to severe HIE, craniofacial, airway 
or foregut malformations or ENT or neuro surgeries. 
Infants who are exclusively breastfeeding are also 
excluded.    
• Test-1: VFSS with concurrent or sequential pharyngo-
esophageal manometry along with standard safety metrics. 
Esophageal and pharyngeal provocation induced 

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aerodigestive reflexes will be tested. Oral feeding challenge 
test is performed during manometry. The same procedures 
without VFSS will be repeated at Time-2 where feasible 
and relevant.   
• Overall Study Endpoints: Primary endpoint is therapeutic 
success defined as full oral feeding without symptoms 
requiring intervention at 4 weeks (for outpatient studies and 
those still admitted at 4 weeks) or discharge, whichever is 
earlier. Secondary clinical end points include growth 
velocity and feeding outcomes at 1 year.  
• Methods to overcome Potential Confounders: It is NICU 
standard to document in EPIC: i) Daily documentation of 
symptoms, medication use, feeding methods and duration, 
feeding volume and weight, ii) Weekly documentation of 
growth velocity (weight, length, head circumference). 
• Removal and management of subject(s) from protocol: The 
investigator and/or the parent(s) have the right to withdraw 
from study at any time and opt for the standard of care. 
Parent(s) that withdraw their infants from the study therapy 
will be encouraged to continue to remain in the study for all 
follow up evaluations. Those who choose complete 
withdrawal from the study will be encouraged to follow the 
standard of care; wherein, response failures are followed 
until 1st birthday in the multidisciplinary developmental 
follow-up clinic. 
• Intermediate outcome measures (up to 1 yr age):  
Acquisition of feeding and GI milestones during first year 
of life.  
6.2 Describe: 
• Manometry methods have been used concurrent with video, 
submental EMG, RIP, ECG, pulse-oximetry and nasal air 
flow to test basal and adaptive pharyngo-esophageal 
reflexes and sensory-motor characteristics of motility and 
to monitor safety. Concurrent synchronized video 
recordings will be performed to further validate symptoms 
based on objective definition of the esophageal reflexes. 
Documentation of symptom markers can be validated by 
integrating manometry with respiratory inductance 
plethysmography and video. 
• Multimodal esophageal and pharyngeal sensory-motor 
testing protocols: We have developed and extensively used 
these protocols to measure sensory-motor characteristics of 

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reflexes, and these testing protocols will be performed as 
validated and reported 
• The source records that will be used to collect data about 
subjects will be EPIC records, patient diary logs for 
symptoms, feeding process, medication compliance, 
physician visits and clinical data.  
6.3 
Data to be collected 
• Patient demographics, feeding and growth outcomes, length of 
hospital stay and comorbidities will be collected from parents and 
from medical records. Basal manometry data will be collected to 
assess the mechanisms of normal or abnormal swallowing. 
Multimodal sensory motor testing involves mid-esophageal 
provocation with graded infusions (0.1 to 5 ml) of air (to stimulate 
mechanoreceptors), apple juice (pH 3.7, to stimulate acid-sensitive 
receptors), and sterile water (pH 7.0, as control stimulus), and 
examine the changes in sensory-motor characteristics of 
aerodigestive reflexes. Basal and adaptive pharyngeal reflexes with 
air and water infusions are measured. 
6.4 Long term follow-up will include feeding method, growth 
characteristics and development up to 1 year of age. 
7.0 
Sharing of Results with Subjects* 
7.1 Manometry results are shared with the parents at the time of the 
study. Parents decide on their preferred feeding approach (flow 
change, thickener change, no change) and if the patient is inpatient, 
this is shared with the medical team.  
8.0 
Study Timelines* 
8.1 Describe: 
• 
The individual subject’s participation in the study will last < 4 
weeks. Data will be collected for the first year of life. 
• 
The duration anticipated to enroll all study subjects is between 
2/16 until 7/20. 
• 
The estimated date to complete this study (complete primary 
analyses) is 12/20. 
9.0 
Inclusion and Exclusion Criteria* 
9.1 All infants < 6 months PMA who are scheduled for a VFSS will be 
screened for the above eligibility criteria. 
9.2 All subjects who consent and receive a concurrent or sequential 
VFSS and esophageal manometry will be included in the analysis. 
9.3 Our population will include individuals who are not yet adults 
(infants) 

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10.0 Vulnerable Populations* 
10.1 This research complies with 45 CFR 46, as it includes only human 
infants up to 6 months old. As this study involves slightly greater 
than minimal risk, as regulated in 45 CFR 46 Subpart D, all subjects 
for this study will have consent of at least one parent. 
• The Neonatal and Infant Feeding Disorders (NIFD) 
Program is directed by the PI, Dr. Sudarshan Jadcherla who 
is a Neonatologist with Pediatric GI experience and is a 
recognized GI motility expert.  The NIFD program is a 
nationally recognized clinical program supported by the 
NIH and is well equipped to conduct clinical studies such 
as proposed in this application. In addition, there is a team 
of dedicated trained nurse coordinators who are competent 
and comfortable with performing these procedures on 
preterm infants as well as a neonatal nurse practitioner. The 
team also includes trained technical personnel affiliated to 
this program who perform these studies on a regular basis 
for diagnostic purposes in this same population. 
11.0 Local Number of Subjects 
11.1 60 subjects 
12.0 Recruitment Methods 
12.1 Parents of infants scheduled for a VFSS who meet the eligibility 
requirements will be approached 
12.2 Subjects will be recruited from the VFSS schedule at NCH. 
12.3 RN Coordinators will identify and screen potential subjects. 
12.4 There will be a $20 payment for each study completed. 
13.0 Withdrawal of Subjects* 
13.1 Patients will be withdrawn if there are any safety concerns with 
continuing. 
13.2 . If a parent decides to withdraw their infant, follow up data will 
continue to be collected.  
14.0 Risks to Subjects* 
14.1 This study includes the risk associated with the nasal placement of 
the manometry probe and the infusion catheter. These risks are 
similar to the risks associated with the placement of a nasogastric 
feeding tube in infants which is frequently done for tube feeding 
infants both in the hospital and sometimes at home. 

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15.0 Potential Benefits to Subjects* 
15.1 The addition of the esophageal manometry to the VFSS will provide 
added information as to the etiology of the infants feeding problem. 
This can be used to improve treatment options and possibly improve 
outcomes. 
16.0 Data Management* and Confidentiality 
16.1 Data Analysis Plan 
•  Descriptive statistics will be reported as median (IQR), 
mean ± SD or total number and percentage for 
demographics and clinical characteristics. For  PPG vs 
FOD historical control comparisons, two-sample t-test or 
ANOVA will be used for the continuous variables and chi-
squared or Fischer’s exact tests will be used for the 
categorical variables, whichever is appropriate. Non-
parametric method (e.g. Wilcoxon) might be used if the 
data is not normally distributed. Normality will be assessed 
using Shapiro-Wilks test and visually inspection of the 
data. For other Normal vs Abnormal VFSS and the effect 
of parent preferred therapy -flow modification or thickener 
use) comparisons, due to the nature of the repeated measure 
of the data, repeated measure ANOVA for continues 
measured variables and Generalized estimating equation 
(GEE) for categorical variables, to predict the likelihood of 
the specific response, will be used as to make the between 
group comparisons. Compound symmetry (CS) will be 
specified for the covariance structure of the repeated data. 
Bonferroni correction will be used to conserve the overall 
type I error at =0.05. To characterize the association 
between the disease comorbidities and feeding success, 
simple and multiple logistic regression analysis will be 
performed. Statistical Analysis Software, version 9.4 (SAS 
Institute Inc., Cary, NC, USA) 
16.2 Data will be stored in RedCap and each subject will have a file 
which is kept in a secured locked location. 
16.3 Data will be verified by at least two individuals on the study team 
17.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
17.1 Describe: 
• 
The study is overseen by an IRB at NCH where safety is 
reviewed on a quarterly basis for the enrolled subjects 
18.0 Provisions to Protect the Privacy Interests of Subjects 

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18.1 Parents will have the choice of whether to participate and share 
information about their child. 
18.2 The research team will access electronic records for follow up data. 
19.0 Compensation for Research-Related Injury 
19.1 Research related injury will not be compensated 
19.2 
Language from Consent: 
• If your child is hurt by the procedures that are part of the 
Study, they will be monitored and treated as needed by the 
study team which includes a physician and a nurse. If there 
is concern for injury after the procedure, you should seek 
medical treatment for the injuries and call the study team as 
soon as possible at the number on page1 of this form.  If it 
is an emergency, call 911 or go to the nearest emergency 
department. In most cases, this care will be billed to your 
health insurance company or whoever usually pays for your 
health care at the usual charges, but some insurance 
companies will not pay for care related to a study.  If the 
care is provided at Nationwide Children's Hospital, we 
make no commitment to pay for the medical care provided 
to you.  No funds have been set aside to compensate you in 
the event of injury.  If no one else pays for your care, you 
may have to pay for the cost of this care.  This does not 
mean that you give up any of your legal rights to seek 
compensation for your injuries. 
20.0 Economic Burden to Subjects 
20.1 None 
21.0 Consent Process 
21.1 Consent 
• 
Consent will take place in person with one parent (risk level 2) 
prior to the study taking place.  
• 
We will be following “SOP: Informed Consent Process for 
Research (HRP-090).”  
Non-English Speaking Subjects – if known, skip if not known 
• 
If subjects do not speak English are enrolled, the consent form 
will be translated in person by an interpreter speaking the 
language of the parent. 
Subjects who are not yet adults (infants, children, teenagers) 

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• 
All subjects enrolled in this study will be infants.  
• 
Parental permission will be obtained from one parent only as 
this study is level 2 risk. 
• 
Consent will not be obtained from individuals other than 
parents. 
22.0 Process to Document Consent in Writing 
22.1 We will be following “SOP: Written Documentation of Consent 
(HRP-091).”  
23.0 Setting 
23.1 The research will be conducted at Nationwide Children’s Hospital, 
Columbus, Ohio. 
• 
Subjects will be recruited from the VFSS schedule at NCH. 
• 
Research procedures will be performed at NCH. 
We will be monitoring safety through an IRB at NCH. 
24.0 Multi-Site Research* 
24.1 Dr. Wei is a Research Assistant Professor at the Department of 
Biostatistics at The Ohio State University College of Medicine and 
Public Health. She has expertise in clinical statistical modeling 
techniques. She has worked with the PI with sample size and 
statistical design for this study. She will provide consultation with 
analysis and design support. Dr. Wei works with the PI closely with 
regards to statistical outputs and manuscript writing.  
24.2  Data is stored in RedCap where all of the study staff including Dr. 
Wei can access the data. Subject identifiers include Names, Birth 
Date, Discharge Date and Medical Record Numbers as identified in 
the consent form. 
25.0  Protected Health Information Recording 
 
Indicate which subject identifiers will be recorded for this research. 
☒  Name 
☐  Complete Address 
☐  Telephone or Fax Number 
☐  Social Security Number (do not check if only used for ClinCard) 
☒  Dates (treatment dates, birth date, date of death) 
☐  Email address, IP address or url 
☒  Medical Record Number or other account number 
☐  Health Plan Beneficiary Identification Number 
☒  Full face photographic images and/or any comparable images (x-rays) 
☐  Account Numbers 

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☐  Certificate/License Numbers 
☐  Vehicle Identifiers and Serial Numbers (e.g. VINs, License Plate Numbers) 
☐  Device Identifiers and Serial Numbers 
☐  Biometric identifiers, including finger and voice prints 
☐  Other number, characteristic or code that could be used to identify an 
individual 
☐  None (Complete De-identification Certification Form) 
 
2.0   
Check the appropriate category and attach the required form* on the Local 
Site Documents, #3. Other Documents, page of the application.  (Choose one.) 
☒  Patient Authorization will be obtained. (Include the appropriate HIPAA 
language (see Section 14 of consent template) in the consent form OR attach 
the HRP-900, HIPAA AUTHORIZATION form.) 
☐  Protocol meets the criteria for waiver of authorization. (Attach the HRP-901, 
WAIVER OF HIPAA AUTHORIZATION REQUEST form.) 
☐  Protocol is using de-identified information. (Attach the HRP-902, DE-
IDENTIFICATION CERTIFICATION form.) (Checked "None" in 1.0 above) 
☐  Protocol involves research on decedents. (Attach the HRP-903, RESEARCH 
ON DECEDENTS REQUEST form.) 
☐  Protocol is using a limited data set and data use agreement. (Contact the 
Office of Technology Commercialization to initiate a Limited Data Use 
Agreement. 
 
*Find the HIPAA forms in the IRB Website Library, Templates. 
 
Attach the appropriate HIPAA form on the “Local Site Documents, #3. 
Other Documents”, page of the application. 
 
3.0    How long will identifying information on each participant be maintained? 
 
4.0 
Describe any plans to code identifiable information collected about each 
participant. 
 
5.0 
Check each box that describes steps that will be taken to safeguard the 
confidentiality of information collected for this research: 
X Research records will be stored in a locked cabinet in a secure location 
X  Research records will be stored in a password-protected computer file 
The list linking the assigned code number to the individual subject will be      
maintained separately from the other research data 
X  Only certified research personnel will be given access to identifiable                                       
subject information 
 
6.0 
Describe the provisions included in the protocol to protect the privacy 
interests of subjects, where "privacy interests" refer to the interest of 
individuals in being left alone, limiting access to them, and limiting access to 

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their information. (This is not the same provision to maintain the 
confidentiality of data.) 
 
Confidential Health Information 
 
1.0 
Please mark all categories that reflect the nature of health information to be 
accessed and used as part of this research. 
 
☒  Demographics (age, gender, educational level) 
☒  Diagnosis 
☒  Laboratory reports 
☒  Radiology reports 
☒  Discharge summaries 
☒  Procedures/Treatments received 
☒  Dates related to course of treatment (admission, surgery, discharge) 
☐  Billing information 
☐  Names of drugs and/or devices used as part of treatment 
☐  Location of treatment 
☐  Name of treatment provider 
☐  Surgical reports 
☒  Other information related to course of treatment 
☐  None 
 
2.0 
Please discuss why it is necessary to access and review the health information 
noted in your response above. 
2.1 
We will be looking at outcome variables for the first year of life 
 
3.0 
Is the health information to be accessed and reviewed the minimal necessary to 
achieve the goals of this research?  ☒ Yes    ☐ No 
 
4.0 
Will it be necessary to record information of a sensitive nature?  ☐ Yes   ☒ No 
 
5.0 
Do you plan to obtain a federally-issued Certificate of Confidentiality as a means 
of protecting the confidentiality of the information collected?  ☐ Yes   ☒ No