Open Label, Compassionate Use Protocol of an Intravenous Fish Oil Emulsion in Infants With Cholestasis
Phase: PHASE1
Conditions: Parenteral Nutrition Associated Cholestasis
Sponsor: Arthur J De Lorimier

Version date 1/12/2018 
 
Title of project: 
Use of an intravenous fish oil emulsion in infants with cholestasis 
 
 
Sponsored by: 
N/A 
 
 
Pharmaceutical Support Provided by:  [if applicable] 
N/A 
 
IND # or non-IND Protocol [Select one] 
N/A – IND# to be obtained from FDA if a patient qualifies for study 
 
Protocol Chair/Principal Investigator: 
Arthur J. de Lorimier 
Protocol Co-Chair(s)/PIs: 
N/A 
Protocol Vice Chair(s): [if applicable] 
N/A 
Clinical Trials Specialist: [if applicable] 
N/A 
DRAFT Version 0.1 
03/11/11 

Version date 1/12/2018 
 
CONTENTS 
 
 
 
Page 
 
SITES PARTICIPATING IN THE STUDY ........................................................................ 4 
PROTOCOL TEAM ROSTER ......................................................................................... 5 
STUDY MANAGEMENT ................................................................................................. 6 
ACRONYMS/ABBREVIATIONS ....................................... Error! Bookmark not defined. 
SCHEMA ......................................................................................................................... 6 
1.0 
HYPOTHESIS AND STUDY OBJECTIVES.......................................................... 7 
1.1 
Hypothesis ................................................................................................. 7 
1.2 
Primary Objective(s) .................................................................................. 7 
1.3 
Secondary Objectives ................................. Error! Bookmark not defined. 
1.4 
Substudy Objectives ................................... Error! Bookmark not defined. 
2.0 
INTRODUCTION .................................................................................................. 7 
2.1 
Background ................................................................................................ 7 
2.2 
Rationale ..................................................... Error! Bookmark not defined. 
3.0 
STUDY DESIGN ................................................................................................. 11 
4.0 
SELECTION AND ENROLLMENT OF SUBJECTS ............................................ 11 
4.1 
Inclusion Criteria ...................................................................................... 11 
4.2 
Exclusion Criteria ..................................................................................... 11 
4.3 
Study Enrollment ProceduresG ............................................................... 11 
4.4 
Substudy Enrollment Procedures (as required)Error! Bookmark not defined. 
4.5 
Coenrollment Guidelines (as required) ....... Error! Bookmark not defined. 
5.0 
STUDY TREATMENT (OR INTERVENTION) .................................................... 11 
5.1 
Regimens (or Intervention), Administration, and Duration ....................... 11 
5.2 
Study Product Formulation and Preparation ............................................ 12 
5.3 
Product Supply, Distribution, and Accountability ...................................... 12 
5.4 
Concomitant Medications ......................................................................... 13 
5.5 
Adherence Assessment (as required) ......... Error! Bookmark not defined. 
6.0 
CLINICAL AND LABORATORY EVALUATIONS .. Error! Bookmark not defined. 
6.1 
Schedule of Events ..................................... Error! Bookmark not defined. 
6.2 
Timing of Evaluations............................................................................... 14 
6.3 
Instructions for Evaluations ......................... Error! Bookmark not defined. 
7.0 
CLINICAL MANAGEMENT ISSUES ................................................................... 14 
7.1 
Toxicity ..................................................................................................... 14 
7.2 
Other Diseases ........................................................................................ 15 
7.3 
Pregnancy ................................................................................................ 15 

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7.4 
Breast-feeding (if applicable) ................................................................... 15 
8.0 
CRITERIA FOR DISCONTINUATION ................................................................ 15 
8.1 
Permanent Treatment Discontinuation .................................................... 15 
8.2 
Premature Study Discontinuation ............................................................ 15 
9.0 
STATISTICAL CONSIDERATIONS .................................................................... 15 
9.1 
General Design Issues............................................................................. 15 
9.2 
Endpoints ................................................................................................. 16 
9.3 
Randomization and Stratification ............................................................. 16 
9.4 
Sample Size and Accrual ......................................................................... 16 
9.5 
Monitoring ................................................................................................ 16 
9.6 
Analyses .................................................................................................. 16 
10.0 PHARMACOLOGY PLAN .................................................................................. 16 
10.1 Pharmacology Objectives ........................... Error! Bookmark not defined. 
10.2 Pharmacology Study Design ....................... Error! Bookmark not defined. 
10.3 Primary and Secondary Data, Modeling, and Data AnalysisError! Bookmark not define
10.4 Anticipated Outcomes ................................. Error! Bookmark not defined. 
11.0 DATA COLLECTION AND MONITORING AND ADVERSE EVENT 
REPORTING ...................................................................................................... 16 
11.1 Records to Be Kept .................................................................................. 16 
11.2 Role of Data Management ....................................................................... 16 
11.3 Clinical Site Monitoring and Record Availability ....................................... 17 
11.4 Expedited Adverse Event Reporting to  ................................................... 17 
12.0 HUMAN SUBJECTS ........................................................................................... 17 
12.1 Institutional Review Board (IRB) Review and Informed Consent ............. 17 
12.2 Subject Confidentiality ............................................................................. 17 
12.3 Study Discontinuation .............................................................................. 17 
13.0 PUBLICATION OF RESEARCH FINDINGS ....................................................... 18 
14.0 BIOHAZARD CONTAINMENT .............................. Error! Bookmark not defined. 
15.0 REFERENCES ................................................................................................... 19 
APPENDIX I .................................................................................................................. 20 
 

 
4 
 
 
SITES PARTICIPATING IN THE STUDY 
 
Sites Participating in the Study [remove Main if no substudy] 
UC-Davis 
 

 
Version date 1/12/2018 
PROTOCOL TEAM ROSTER 
Chair Arthur J. de Lorimier 
Co-Chairs No 
Vice Chair(s) No 
 Clinical Representative No 
Clinical Trials Specialist No 
 
Statistician(s) No 
Scientific Committee Representative (if 
assigned) No 
Data Manager No 
Pharmacist No 
Field Representative No 
Laboratory Technologist No 
Laboratory Data Coordinator No 

 
Version date 1/12/2018 
STUDY MANAGEMENT 
 
SCHEMA 
 
Use of an intravenous fish oil emulsion in infants with cholestasis 
 
 
DESIGN Observational, compassionate use, single cohort study 
DURATION Open 
SAMPLE SIZE 25 
POPULATION Infants less than 12m of age at time of recruitment 
STRATIFICATION (as required) N/A 
REGIMEN OR INTERVENTION (as required) N/A 
SUBSTUDIES (as required) N/A 

 
Version date 1/12/2018 
1.0 
HYPOTHESIS AND STUDY OBJECTIVES 
1.1 
Hypothesis 
Use of omegaven in infants with cholestasis will be temporally related to resolution of 
cholestasis. 
 
1.2 
Primary Objective(s)  
The aims of the study are to assess the effect of intravenous fish oil emulsion 
(omegaven) in place of the currently used intravenous soybean oil lipid emulsion 
(Intralipid) in subjects with short bowel syndrome and cholestasis or with PNALD 
(parenteral nutrition associated liver disease). 
 
2.0 
INTRODUCTION 
2.1 
Background 
Functional short gut (or short bowel syndrome, SBS) is defined as the inability to 
tolerate all nutritional requirements via the enteral route, and a continuing dependence 
of partial or complete parenteral nutrition. 
 
Development of SBS (short bowel syndrome) is more common in newborn infants than 
at any other age group, and may result from gastroschisis, gastrointestinal atresia, 
intestinal volvulus, or necrotizing enterocolitis. Treatment is aimed at: 
 
1. Nutritional support, through the use of parenteral nutrition. 
2. Gut rehabilitation and adaptation through gradual introduction and advancement 
of enteral feeds. 
3. Prevention of secondary problems (e.g. bile acid deficiency or bacterial 
overgrowth). 
4. Prevention of complications (e.g. cholestasis). 
 
Concerted, coordinated management, including parenteral nutrition, has greatly 
improved the survival and quality of life of subjects with SBS. However, prolonged use 
of parenteral nutrition is not without risk. Parenteral nutrition associated cholestasis 
(PNAC); also know as parenteral nutrition associated liver disease (PNALD) or intestinal 
failure associated liver disease (IFALD); is one of the leading causes of death in SBS.  
 
The causes of PNALD are unclear, but may include: 
 
1. Absence of enteral feeds. 
2. “Toxic” components in parenteral nutrition (e.g. aluminium, phytosterols, 
methionine, tryptophan). 
3. Lack of certain beneficial nutrients in parenteral nutrition (e.g. serine, choline). 
 
In recent years, much attention has been paid to the effect of parenteral lipid on PNAC. 
In the US, parenteral lipids are vegetable-based. Most widely used is Intralipid with is 

 
Version date 1/12/2018 
a mixture of soybean oil and egg phospholipids. Although it has a generally excellent 
short- and long-term safety record, there are concerns about its long term use. As it is 
vegetable based is contains relatively high amounts of phytosterols (cholesterol-like 
lipids derived from plants). In adults and children with SBS and PNAC, serum levels of 
phytosterols correlate with the degree of hepatic and biliary dysfunction. 
 
Omegaven is a fish-oil derived intravenous lipid emulsion that is not licensed in the US, 
but is widely used in Europe. It differs in composition from intralipid in many ways, for 
example it is much higher in omega-3 fats, lower in omega-6 fats, and contains no 
phytosterols. 
 
Composition of Different iv lipid emulsions (from Puder 2009) 
 
 
There are an increasing number of case-control studies suggesting significant clinical 
benefits to the use of omegaven in established PNALD in infants (Gura 2006, Gura 
2008, Diamond 2009, Puder 2009). 
 
The largest of these published cohorts is that of Puder, from Boston Children’s Hospital 
(see attached file). In that study 42 infants who developed PNALD on standard 
intravenous lipid emulsions were given omegaven, and compared to 49 historical 
controls. Subjects were eligible for omegaven if they had cholestasis (direct bilirubin ≥ 2 
mg/dL), were likely to be on parenteral nutrition at least 30d, and had acquired or 
congenital GI disease. Subjects with cystic fibrosis, metabolic disorders or hepatitis C 
were excluded. They were compared to historical controls who had two consecutive 
direct bilirubin measurements ≥ 2 mg/dL. Omegaven was given at a dose of 1 g/kg/d, 
and intalipid at 1-4 g/kg/d (depending on attending preference and lipid tolerance). The 
fish oil group were generally more sick at study entry than the historical controls, they 
had been on parenteral nutrition longer (63d vs. 40d, p=0.008) and their direct bilirubin 
was higher (5.5 vs. 3.3, p=0.0003). Despite these baseline differences, the fish oil group 
had a steady and sustained fall in direct bilirubin and ALT, while these measures 
continued to increase in the historical controls. 

 
Version date 1/12/2018 
 
Figure Direct bilirubin and ALT in the fish oil group, and the historical controls (from 
Puder 2009). 
 
 
 
Cholestasis resolved in 45% (19/42) of the fish oil group while still on PN, compared to 
4% (2/46) of the historical cohorts. 
 
The rate of the combined outcome of death or required liver transplant was significantly 
lower in the fish oil group (9.5%) than in the historical controls (34.7%, p=0.0005). The 
crude rate of reversal of cholestasis in subjects who did not die or require liver 
transplants was 8.6x greater in the fish oil group than in the historical controls. This 
increased to 17.4x higher rate once differences in baseline characteristics were 
accounted for. 
 
The main safety measures followed (hypertriglyceridemia, and coagulopathy) 
significantly favored the fist oil group. 
 

 
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Table Incidence of hypertriglyceridemia and coagulopathy in fish oil group, and the 
historical controls (from Puder 2009). 
 
 
Although there was no significant difference in INR between the groups over the entire 
study, INR began to increase in the controls near the end of the study as they 
developed worsening end-stage liver disease. In the fish oil group, INR remained low 
during the entire study. 
 
Figure INR in the fish oil group, and the historical controls (from Puder 2009). 
 
 
References 
Puder 2009. Parenteral fish oil improves outcomes in patients with parenteral nutrition-
associated liver injury. Ann Surg 2009;250:395-402. 
Gura 2006. Reversal of parenteral nutrition-associated liver disease in two infants with 

 
Version date 1/12/2018 
short bowel syndrome using parenteral fish oil: implications for future management. 
Pediatrics 2006;118:e197-201. 
Gura 2008. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of 
parenteral nutrition-associated liver disease. Pediatrics 2008;121:e678-86. 
Diamond 2009. Changing the paradigm: omegaven for the treatment of liver failure in 
pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2009;48:209-15. 
 
 
3.0 
STUDY DESIGN 
Compassionate use, single cohort, observational study. 
 
4.0 
SELECTION AND ENROLLMENT OF SUBJECTS 
4.1 
Inclusion Criteria 
Infants on parenteral nutrition who have congenital or acquired gastrointestinal diseases 
that place them at risk of short bowel syndrome (SBS) or prolonged parenteral-nutrition-
dependence, will be considered eligible for the study if either (1) they remain cholestatic 
(bilirubin > 2 mg/dL) after 4wks of reduced lipids and trace elements, or (2) If their direct 
bilirubin is > 6 mg/dL in the absence of suspected or proven infection.    
4.2 
Exclusion Criteria 
Subjects will be considered ineligible for the study if they are felt unlikely to survive 
more than 30d, or unlikely to require parenteral nutrition for at least 30d. 
 
4.3 
Study Enrollment Procedures 
Clinical nutrition rounds, between the PI and the NICU dietician, occur every 1-2wk as 
part of the routine clinical care of the infants. As part of the clinical care of the infants, 
and infant identified as having cholestasis or PNALD (direct bilirubin ≥2 mg/dL on two 
consecutive occasions ≥8d apart) have their intralipid infusion rate reduced to 1 g/kg/d 
and have the trace elements added to their parenteral nutrition reduced. The current 
protocol will not alter this. 
 
5.0 
STUDY TREATMENT (OR INTERVENTION) 
5.1 
Regimens (or Intervention), Administration, and Duration 
The intervention is the use of omegaven (an intravenous fish oil emulsion) in place of 
intralipid (the currently used soybean oil intravenous lipid emulsion, until parenteral 
nutrition is discontinued, or until cholestasis resolves. 
 
Parents of eligible patients will be approached for consent for their infants to take part in 
the study. If they agree, the PI will contact the FDA to receive an IND number for the 
infant (copies of the required FDA paperwork will be sent to the IRB). Omegaven will be 
ordered from the manufacturer. Once the IND number is received, the IRB will be 
informed of the subjects IND number. Once the IND number is received, and 
communicated with the IRB, and the omegaven is received, intralipid infusions will be 

 
Version date 1/12/2018 
stopped and omegaven will be infused at the rate of 1 g/kg/d. Clinically-indicated labs 
will be monitored, as for all patients on prolonged parenteral nutrition, i.e. CBC, 
electrolytes, BUN, Creatinine, ALT, AST, Alkaline phosphatase, albumin, total bilirubin, 
direct bilirubin and serum triglycerides will be measured at least every 2 weeks. No 
additional labs will be required as part of the study. 
 
Adjustment of Omegaven Dosage 
Hypertriglyceridemia: If serum triglycerides are > 400, other causes will be excluded 
(e.g. renal disease, medications). If no other causes can be found, the clinical team 
caring for the baby may decide to reduce the infusion of omegaven by 25%, depending 
on their clinical assessment of risk and benefits. 
Essential Fatty Acid Deficiency: If there are concerns that essential fatty acid deficiency 
may be occurring (characteristic skin rash plus unexplained thrombocytopenia), the 
clinical team caring for the baby may decide to discontinue omegaven and re-start 
infusion of intralipid at a rate of 0.5 – 1 g.kg/d. 
Other: The clinical team caring for the baby will be allowed to withhold the omegaven 
infusion or restart the intralipid infusion for any reason if they believe that to be in the 
best interests of the patient. 
 
Discontinuation of Omegaven 
Omegaven will be discontinued either (1) once parenteral nutrition is discontinued, 
irrespective of the direct bilirubin level, or (2) once the direct bilirubin has been below 2 
mg/dL for more than 2weeks. In the later case, if the direct bilirubin rebounds above 2 
mg/dL at anytime the omegaven can be restarted. If omegaven is re-started, the 
discontinuation criteria will be the same as before: i.e. it will be discontinued when 
parenteral nutrition is discontinued or when the direct bilirubin has been below 2 mg/dL 
for more than 2 weeks. 
 
Safety Assessment 
Routine clinical labs will be used to monitor for the principal side effects of omegaven 
(thrombocytopenia, hypertriglyceridemia), and the response to treatment (direct 
bilirubin, ALT). INR and triene:tetrene ratio will be assessed as clinically indicated if 
coagulopathy or essential fatty acid deficiency are suspected. 
 
5.2 
Study Product Formulation and Preparation 
Omegaven intravenous lipid emulsion as supplied by the manufacturer. 
 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability 
 
5.3.1 Study Product Acquisition 
Parents of eligible patients will be approached for consent for their infants to take part in 
the study. If they agree, the PI will contact the FDA to receive an IND number for the 
infant (copies of the required FDA paperwork will be sent to the IRB). Omegaven will be 
ordered from the manufacturer. Once the IND number is received, the IRB will be 

 
Version date 1/12/2018 
informed of the subjects IND number. Once the IND number is received, and 
communicated with the IRB, and the omegaven is received, intralipid infusions will be 
stopped and omegaven will be infused at the rate of 1 g/kg/d. 
5.3.2 Study Product Accountability 
The FDA permits the cost of omegaven to be billed to insurance carriers, or to public 
insurance. These costs will be largely, but not completely offset by the reduction in cost 
as the standard intravenous lipid (intralipid) will not be given. No addition laboratory 
tests will be carried out. If the relevant private or public insurance provider refuses to 
cover the additional cost of omegaven (approx $50-75/d) we would expect that costs will 
be absorbed by either the UCDMC pharmacy. In the unlikely event that this does not 
prove possible, and alternative coverage for omegaven can not be found (e.g. internal 
NICU funds) the parents will be asked to pay for omegaven. The IRB will be informed of 
this eventuality should it occur. The consent form will clearly state the plans regarding 
charging for omegaven, and that the family would be payers of last resort if alternative 
methods of funding the omegaven are not successful. 
 
5.4 
Concomitant Medications 
5.4.1 Required Medications 
Current receipt of parenteral nutrition (including iv lipids), are required for the diagnosis 
of PNALD, and therefore for enrollment in the study 
5.4.2 Prohibited Medications 
None 
5.4.3 Precautionary Medications 
None 
 
 
6.0 
CLINICAL AND LABORATORY EVALUATIONS

 
Version date 1/12/2018 
6.2 
Timing of Evaluations 
 
6.2.1 Screening and Pre-Entry Evaluations  
Clinical nutrition rounds, between the PI and the NICU dietician, occur every 1-2wk as 
part of the routine clinical care of the infants. As part of the clinical care of the infants, 
and infant identified as having cholestasis or PNALD (direct bilirubin ≥2 mg/dL on two 
consecutive occasions ≥8d apart) are identified. 
6.2.2 Entry Evaluations 
Clinical nutrition rounds, between the PI and the NICU dietician, occur every 1-2wk as 
part of the routine clinical care of the infants. As part of the clinical care of the infants, 
and infant identified as having cholestasis or PNALD (direct bilirubin ≥2 mg/dL on two 
consecutive occasions ≥8d apart) have their intralipid infusion rate reduced to 1 g/kg/d 
and have the trace elements added to their parenteral nutrition reduced. The current 
protocol will not alter this. If they remain cholestatic (bilirubin > 2 mg/dL) after 4wks of 
reduced lipids and trace elements, or (2) if their direct bilirubin is > 6 mg/dL in the 
absence of suspected or proven infection they will be considered eligible for the study. 
6.2.3 Post-Entry Evaluations 
Will continue as part of the clinical nutrition rounds 
6.2.4 Discontinuation Evaluations 
Will continue as part of the clinical nutrition rounds. Omegaven will be discontinued 
either (1) once parenteral nutrition is discontinued, irrespective of the direct bilirubin 
level, or (2) once the direct bilirubin has been below 2 mg/dL for more than 2 weeks. In 
the later case, if the direct bilirubin rebounds above 2 mg/dL at anytime the omegaven 
can be restarted. If omegaven is re-started, the discontinuation criteria will be the same 
as before: i.e. it will be discontinued when parenteral nutrition is discontinued or when 
the direct bilirubin has been below 2 mg/dL for more than 2 weeks. Omegaen may also 
be discontinued at any time is desired by the family, the attending physician or the study 
PI. 
7.0 
CLINICAL MANAGEMENT ISSUES 
7.1 
Toxicity  
Routine clinical labs will be used to monitor for the principal side effects of omegaven 
(thrombocytopenia, hypertriglyceridemia), and the response to treatment (direct 
bilirubin, ALT). INR and triene:tetrene ratio will be assessed as clinically indicated if 
coagulopathy of essential fatty acid deficiency are suspected. If serum triglycerides are 
> 400, other causes will be excluded (e.g. renal disease, medications). If no other 
causes can be found, the clinical team caring for the baby may decide to reduce the 
infusion of omegaven by 25%, depending on their clinical assessment of risk and 
benefits. If there are concerns that essential fatty acid deficiency may be occurring 

 
Version date 1/12/2018 
(characteristic skin rash plus unexplained thrombocytopenia), the clinical team caring 
for the baby may decide to discontinue omegaven and re-start infusion of intralipid at a 
rate of 0.5 – 1 g/kg/d. 
 
An external Data Safety Monitor (Dr. Steven A. Abrams, Professor of Pediatrics, Section 
of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas 
Children’s Hospital, Houston, TX) will be informed of all subjects recruited to the 
protocol. He will be informed, by e-mail, of any laboratory results on the subjects at least 
monthly, or within 7d of any significant change in biochemical data. He will have the 
authority to withdraw a subject from the protocol at any time. He will be unaware of the 
subjects name, but will be made aware of any pertinent clinical data relevant to lab 
interpretation (e.g. presence or absence of infection, underlying GI diagnosis, amount of 
enteral feeds etc). Subjects will be identified by an anonymous number when 
communicating with the external safety monitor. 
 
7.2 
Other Diseases 
N/A 
 
7.3 
Pregnancy 
N/A 
 
7.4 
Breast-feeding (if applicable) 
N/A 
 
8.0 
CRITERIA FOR DISCONTINUATION 
8.1 
Permanent Treatment Discontinuation 
Omegaven will be discontinued either (1) once parenteral nutrition is discontinued, 
irrespective of the direct bilirubin level, or (2) once the direct bilirubin has been below 2 
mg/dL for more than 2 weeks. In the later case, if the direct bilirubin rebounds above 2 
mg/dL at anytime the omegaven can be restarted. If omegaven is re-started, the 
discontinuation criteria will be the same as before: i.e. it will be discontinued when 
parenteral nutrition is discontinued or when the direct bilirubin has been below 2 mg/dL 
for more than 2 weeks. 
 
8.2 
Premature Study Discontinuation 
As for 8.1 
 
9.0 
STATISTICAL CONSIDERATIONS 
9.1 
General Design Issues 
This is a compassionate use, non-hypothesis testing protocol. Summary descriptive 
statistics will be generated, e.g. time to resolution of cholestasis. 
 

 
Version date 1/12/2018 
9.2 
Endpoints 
 
9.2.1 Primary Endpoints (including definitions) 
Time to resolution of cholestasis (direct bilirubin < 2 mg/dL without subsequent rebound 
above 2 mg/dL). 
9.2.2 Secondary Endpoints (including definitions) 
None 
9.2.3 Substudy Endpoints (as required) 
None 
9.3 
Randomization and Stratification 
N/A 
 
9.4 
Sample Size and Accrual 
Up to 25 subjects recruited 
 
(For main study and substudies.) 
9.5 
Monitoring 
As above 
 
9.5 
Analyses 
As above 
 
 
10.0 PHARMACOLOGY PLAN 
N/A 
 
11.0 DATA COLLECTION AND MONITORING AND ADVERSE EVENT REPORTING 
11.1 Records to Be Kept 
The patient’s participation will be documented in the EMR. All labs will be measured for 
clinical reasons, not for reasons related to the study. They will stay in the EMR. A list of 
patients on the study will be kept in a secure filing cabinet by the PI. 
 
11.2 Role of Data Management 
N/A. 

 
Version date 1/12/2018 
11.3 Clinical Site Monitoring and Record Availability 
N/A 
 
11.4 Expedited Adverse Event Reporting to  
An external Data Safety Monitor (Dr. Steven A. Abrams, Professor of Pediatrics, Section 
of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas 
Children’s Hospital, Houston, TX) will be informed of all subjects recruited to the 
protocol. He will be informed, by e-mail, of any laboratory results on the subjects at least 
monthly, or within 7d of any significant change in biochemical data. He will have the 
authority to withdraw a subject from the protocol at any time. He will be unaware of the 
subject name, but will be made aware of any pertinent clinical data relevant to lab 
interpretation (e.g. presence or absence of infection, underlying GI diagnosis, amount of 
enteral feeds etc). Subjects will be identified by an anonymous number when 
communicating with the external safety monitor. 
 
The IRB will also be informed of any adverse events. The FDA will be informed of any 
adverse events only to the extent required by law. 
 
12.0 HUMAN SUBJECTS 
12.1 Institutional Review Board (IRB) Review and Informed Consent 
This protocol and the informed consent document (pending) and any subsequent 
modifications will be reviewed and approved by the IRB or ethics committee responsible 
for oversight of the study. A signed consent form will be obtained from the subject (or 
parent, legal guardian, or person with power of attorney for subjects who cannot 
consent for themselves, such as those below the legal age of consent). The consent 
form will describe the purpose of the study, the procedures to be followed, and the risks 
and benefits of participation. A copy of the consent form will be given to the subject, 
parent, or legal guardian, and this fact will be documented in the subject’s record. 
 
12.2 Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified by coded number only to maintain subject confidentiality. All records 
will be kept locked. All computer entry and networking programs will be done with coded 
numbers only. Clinical information will not be released without written permission of the 
subject, except as necessary for monitoring by IRB, the FDA, the , the OHRP, or the 
pharmaceutical supporter(s) or designee. 
12.3 Study Discontinuation 
The study may be discontinued at any time by the IRB, the pharmaceutical supporter(s), 
the FDA, the OHRP, or other government agencies as part of their duties to ensure that 
research subjects are protected.  

 
Version date 1/12/2018 
13.0 PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by policies.  
  

 
Version date 1/12/2018 
15.0 REFERENCES 
Puder 2009. Parenteral fish oil improves outcomes in patients with parenteral nutrition-
associated liver injury. Ann Surg 2009;250:395-402. 
Gura 2006. Reversal of parenteral nutrition-associated liver disease in two infants with 
short bowel syndrome using parenteral fish oil: implications for future management. 
Pediatrics 2006;118:e197-201. 
Gura 2008. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of 
parenteral nutrition-associated liver disease. Pediatrics 2008;121:e678-86. 
Diamond 2009. Changing the paradigm: omegaven for the treatment of liver failure in 
pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2009;48:209-15. 
 
.

 
Version date 1/12/2018 
APPENDIX I 
 
This format will allow the title and first page number of each appendix to appear in the 
Table of Contents. 
 
The Sample Informed Consent will continue to be numbered as it has been (i.e., Page 1 
of X).