Clinical trial NCT04697888
Conditions: Parenteral Nutrition-related Hepatitis
Sponsor: Children's Mercy Hospital Kansas City
Start date: 2013-04-01; Completion date: 2018-11-01
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
To provide parenteral fat emulsion prepared from fish oil (omega-3 fatty acid emulsion, Omegaven®) to patients with liver disease (PNALD).

Detailed description:
This is a compassionate use protocol for patients with PNALD who have failed traditional treatment to receive Omegaven through an IND. Omegaven will be infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition.

Arms: arm 1: Use of Omegaven for patients with parenteral nutrition associated liver disease.
Interventions: intervention 1: Omegaven
Intervention descriptions: intervention 1: Expanded Access Therapy with Omegaven will be initiated at a starting dose of 0.5 gm/kg/day to be infused over 24 hrs. After two days of infusion the dose will be increased to 1gm/kg/day.

Protocol documents:
Prot_000.pdf: 
Omegaven for PNALD 
 
 
 
 
 
 
 
 
 
IRB # 12010063 
 
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Treatment Use of Omegaven for treatment with Parenteral Nutrition Associated Liver 
Disease 
 
Principal Investigator: 
Joel Lim, MD, principal investigator, CMH, Gastroenterology, 234-3017, jdlim@cmh.edu 
 
Co-Investigators: 
Tracy Sandritter, PharmD, sub-investigator, CMH, Pediatric Pharmacology and Medical 
Toxicology, 234-9301, tlsandritter@cmh.edu 
 
Kim Radford, RN, MSN, CPNP-AC, sub-investigator, CMH, Gastroenterology, 983-
6748, kradford@cmh.edu 
 
William San Pablo, MD, sub-investigator, CMH, Gastroenterology, 983-6658, 
wsanpablo@cmh.edu 
 
Walter Andrews, MD, sub-investigator, CMH, Transplant Surgery, 234-3633, 
wandrews@cmh.edu 
 
Rich Hendrickson, MD, sub-investigator, CMH, Transplant Surgery, 983-6335, 
rjhendrickson@cmh.edu 
 
Beth Lyman, RN, CNSN, sub-investigator, CMH, Gastroenterology, 855-1766, 
blyman@cmh.edu 
 
Research Personnel: 
Corey Schurman, MA, coordinator, CMH, Gastroenterology, 802-1167, 
crschurman@cmh.edu 
 
Shawna Ricks, RN, MSN, CCRC, coordinator, CMH, Gastroenterology, 234-3197, 
sricks@cmh.edu 
 
Study Site(s): Children’s Mercy Hospital 
 
Protocol Version:  1.0 
Protocol Date:  1/30/12 
1. STUDY OBJECTIVES/HYPOTHESIS 
Primary Objective 
 
To evaluate whether established parenteral nutrition associated liver disease (PNALD) can be 
reversed or its progression halted by using a parenteral fat emulsion prepared from fish oil 
(omega-3 fatty acid emulsion, Omegaven®) as measured by normalization or decrease of serum 
levels of hepatic enzymes. 
Secondary Objective 


Omegaven for PNALD 
 
 
 
 
 
 
 
 
 
IRB # 12010063 
 
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To assess the safety profile of the intravenous omega-3 fatty acid emulsion (Omegaven®). 
2. BACKGROUND 
 
Patients suffering from short bowel syndrome require life-saving parenteral nutrition 
(PN).  One of the major complications of this essential therapy is PNALD, especially in infants 
and children.  This liver injury affects the majority of infants and children on long term PN and 
may progress to liver failure, liver transplantation or ultimately death. A number of causes of 
PNALD have been proposed, including the use of intravenous fat emulsions. 
PN provides intravenous nutritional supplementation for patients unable to absorb 
adequate enteral nutrients secondary to insufficient intestinal length or decreased functionality.   
PN contains the macronutrient building blocks of the human diet in their most elemental forms 
(amino acids and dextrose) and is commonly administered with a lipid emulsion to avoid essential 
fatty acid deficiency and to provide a calorically dense source of non-protein calories.  In 
addition, PN contains the essential micronutrients (electrolytes, trace elements, and vitamins) to 
provide an optimal nutritional regimen.  Before the development of PN, patients with insufficient 
gastrointestinal absorptive function commonly died of starvation and subsequent complications of 
malnutrition.  Today many patients (30,000) patients are permanently dependent on PN for 
survival.  However, PN continues to be associated with hepatic injury that occurs at an 
unpredictable rate and includes both biochemical (elevated serum aminotransferases and alkaline 
phosphatase) and histological alterations such as steatosis, steatohepatitis, lipidosis, cholestatis, 
fibrosis, and cirrhosis.    
Parenteral lipid emulsions in the United States are soy-based products which are rich in 
omega-6 fatty acids. These emulsions have been implicated in predisposing patients to PNALD 
because of their phytosterol content, which is thought to have a deleterious effect on hepatic 
biliary secretion and cause accumulation of lipids in the liver.  On the other hand, animal studies 
have shown that intravenous fat emulsions prepared from fish oil, which are high in omega-3 
fatty acids, do not impair bile flow and may actually diminish fat accumulation in hepatocytes.  
Fish oil based emulsions (ie, Omegaven) are available in Europe.  Due to regulatory and 
manufacturing limitations, these products are not available to patients in the US unless their 
physician petitions the Food and Drug Administration for permission to import them on a 
compassionate use basis. 
Children’s Hospital, Boston has published data regarding the use of Omegaven in 
patients with PNALD. 
 It has been their experience, that through the use of Omegaven instead of conventional 
lipid emulsions, that the biochemical tests of liver function improved significantly. 
There has been no documented case of heavy metal contamination with the use of 
Omegaven.  There is no discussion in the literature of there being any worry or risk of this 
happening.   
3. DESIGN 
 
This is a compassionate use protocol for patients with PNALD who have failed traditional 
treatment to receive Omegaven through an IND. 
TARGET POPLUATION SPECIFICS 
We will be enrolling up to 10 patients 0- less than18 years of age who have Parenteral Nutrition 
Associated Liver Disease.  These patients will have been on traditional TPN for on average 2-4 


Omegaven for PNALD 
 
 
 
 
 
 
 
 
 
IRB # 12010063 
 
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weeks and will remain on TPN using Omegaven until they no longer need TPN or are sent for 
short bowel or liver transplant. 
Inclusion Criteria 
1. The patient will be PN dependent and unable to meet nutritional needs solely by enteral 
nutrition. 
2. Patient will be <18 years of age. 
3. Direct bilirubin > 2.0mg/dl 
4. The patient must have failed standard therapies to prevent progression his/her liver 
disease. 
Exclusion Criteria 
1. Other causes of chronic liver disease (Hepatitis C, Cystic fibrosis, biliary atresia, and alpha 1 
anti-trypsin deficiency). 
2. Patients who are allergic to eggs/shellfish 
3. Patients who have severe hemorrhagic disorders. 
5. DATA COLLECTION 
Data Collection Procedures 
Patients will be identified by Dr. Lim and the Intestinal Rehabilitation/Transplant Team. 
 
All potential patients will be either inpatient admitted under the GI or Surgery Service, or GI or 
Surgery Services will be consulted. Dr. Lim or one of the sub-investigators will be notified by the 
services (if he is not the attending) that a subject has clinically progressed towards needing the 
investigational drug. Dr. Lim will ultimately decide if a subject meets criteria for enrollment. 
 
When Dr. Lim feels a patient will benefit from Omegaven, he or one of the sub-investigators will 
discuss the protocol with the family and answer all questions.  Permission/assent will be obtained 
by the PI, sub-investigators or coordinator. 
Records to be kept 
All data collection will be part of the patient’s medical record and there is no plan to record any 
additional data.  A patient record will be kept with lab results and other information directly 
related to a subject’s response to Omegaven.  This record will be identified with a unique study 
number and a master linking list will be maintained that links the subject’s medical record 
number to their study number. 
 Secure Storage of Data 
The patient record will consist of an excel spread sheet that will be located in the GI section 
folder on the CMH network.  The linking list will be kept in a separate folder in the GI section 
folder.  Only the PI and coordinators will have access to these folders. 
STUDY DURATION/STUDY TIMELINE 
 
This protocol will be kept open indefinitely for the benefit of patients who have PNALD 
and need access to Omegaven through this IND. 


Omegaven for PNALD 
 
 
 
 
 
 
 
 
 
IRB # 12010063 
 
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STATISTICAL CONSIDERATIONS 
 
As this is a compassionate use protocol, there are no real statistical considerations.  All 
subjects who could benefit from Omegaven will be included.  
Institutional Review Board (IRB) Review and Informed Consent 
This protocol, and any subsequent modifications, will be reviewed and approved by the 
Pediatric IRB at The Children’s Mercy Hospital & Clinics. 
Permission/assent will be obtained after Dr. Lim has decided that a patient would benefit 
from Omegaven therapy and all other standard therapies have been exhausted.  
Permission/assent will be obtained in person and as the subjects will all be inpatients, will 
most likely be obtained in the NICU or PICU.  Without this treatment, the next step for 
these patients is short bowel or liver transplant. 
Subject Confidentiality 
 
All data collection will be part of the patient’s medical record and there is no plan to 
record any additional data.  A research record will be kept with lab results and other 
information directly related to a subject’s response to Omegaven.  This research record 
will be identified with a unique study number and a master linking list will be maintained 
that links the subject’s medical record number to their study number. 
All research records will be kept on an excel spreadsheet in a protected folder which only 
the PI and coordinators will have access to.  There are no patient identifiers recorded in 
the research record. All computer entry and networking programs will be done using 
study identification only.  All data will be entered into a computer that is password 
protected.  All data will be maintained for a minimum of three years after completion of 
the protocol. 
 
Study Modification/Discontinuation 
The protocol may be modified or discontinued at any time by the IRB, the OHRP, the 
FDA or other Government agencies as part of their duties to ensure that patients are 
protected. 
PUBLICATION OF RESEARCH FINDINGS 
 
There are no plans to publish findings, however, there is always the chance that 
something may be found during the course of treatment that would be of scientific merit 
and would be of benefit to add to the literature on Omegaven.