Cholestasis, Parenteral Nutrition Associated Liver Disease PNALD
Conditions
Keywords
PN, parenteral nutrition, fat emulsions, omega-6 fatty acid, liver disease, fatty acid deficiency
Brief summary
The purpose of this study is to determine if established parenteral nutrition (PN) associated liver disease can be reversed or its progression halted by using a parenteral fat emulsion prepared from fish oil as measured by normalization of serum levels of hepatic enzymes and bilirubin.
Detailed description
The primary objective of this study is to evaluate the need for and time to small bowel transplantation or liver transplantation. This will be calculated as both the age at time of primary transplant as well as the length of time from initial evaluation to transplant.Secondary objectives are to determine if there are improvements in clinical measures associated with established parenteral nutrition- associated liver disease (PNALD). These will be determined by measurement of total and direct bilirubin levels, platelet count, serum albumin, and changes in both length and weight growth curves.
Interventions
DRUGOmegaven™
10% Omegaven™, 50 or 100 mL bottle; 1gram/kg/day and is infused over 12-24 hours.
Sponsors
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be enrolled in the Intestinal Rehabilitation Program at the University of Nebraska Medical Center, AND: * Be unable to meet nutritional needs solely by enteral nutrition and be expected to require PN for at least another 30 days * Have clinical evidence of parenteral nutrition associated liver disease (PNALD) as defined as a direct bilirubin of 2 mg/dl or more. A liver biopsy is desirable but not necessary for treatment * Signed patient informed consent
Exclusion criteria
* Parent or guardian or child unwilling to provide consent or assent * Inability or unwillingness on the part of parent/guardian or child to follow clinical recommendations of the Intestinal Rehabilitation Program * Allergies or clinical conditions precluding safe use of Omegaven™
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Progression to Small Bowel Transplantation. | Bi-weekly x4, then monthly until the completion of the study, for an overall average of 5.5 years follow-up for the cohort | Whether or not the subject had an intestine-containing transplant or not |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Reversal of Biochemical Cholestasis | weekly x 4, then bi-weekly x4, then monthly until the completion of the study, with an average follow-up of 5.5 years for the study cohort | Of patients starting with elevated total serum bilirubin, the number that progress to normalization of serum total bilirubin in routine bloodwork |
Countries
United States
Participant flow
Recruitment details
Patient recruitment began May 1, 2008. The study was closed October 6, 2017
Participants by arm
| Arm | Count |
|---|---|
| Omegaven™ This study will be a prospective, non-randomized, open-label study of Omegaven™ for provision of parenteral lipid calories. The study cohort, receiving the PN lipid at 1g/kg/day, will be compared to historical controls at UNMC where parenteral lipid calories were provided exclusively through soybean-based formulations. The study is planned to enroll 100 patients. The Intestinal Rehabilitation Program at UNMC sees between 20 and 30 new pediatric patients per year, with almost all being PN-dependent and over 75% presenting with a bilirubin ≥ 2mg/dL. Based on these calculations, we estimate 4-5 years to enroll 100 patients.
Omegaven™: 10% Omegaven™, 50 or 100 mL bottle; 1gram/kg/day and is infused over 12-24 hours. | 72 |
| Total | 72 |
Baseline characteristics
| Characteristic | Omegaven™ |
|---|---|
| Age, Continuous | 5.8 months STANDARD_DEVIATION 7.3 |
| Alkaline Phosphatase at Treatment Start | 436 U/L STANDARD_DEVIATION 226 |
| Direct Bilirubin (mg/dL) at Treatment Start | 6.2 mg/dL STANDARD_DEVIATION 3.9 |
| Enteral Calories at Treatment Start (kCal/kg/d) | 8 kCal/kg/d STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gestational Age (weeks) | 31 weeks STANDARD_DEVIATION 5 |
| Length (cm) at Treatment Start | 55 cm STANDARD_DEVIATION 10 |
| Length Z Score at Treatment Start | -2.09 z score STANDARD_DEVIATION 2.17 |
| Parenteral Nutrition (PN) Calories at Treatment Start (kCal/kg/d) | 91 kCal/kg/d STANDARD_DEVIATION 11 |
| Serum alanine aminotransferase (ALT) at treatment Start | 159 U/L STANDARD_DEVIATION 125 |
| Serum aspartate aminotransferase (AST) at Treatment Start | 187 U/L STANDARD_DEVIATION 137 |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 43 Participants |
| Total Bilirubin (mg/dL) at Treatment Start | 9.9 mg/dL STANDARD_DEVIATION 6.2 |
| Underlying Diagnosis Gastroschisis | 22 Participants |
| Underlying Diagnosis Intestinal Aganglionosis | 1 Participants |
| Underlying Diagnosis Intestinal Atresia | 8 Participants |
| Underlying Diagnosis Mesenteric Ischemia | 1 Participants |
| Underlying Diagnosis Microvillus inclusion disorder | 4 Participants |
| Underlying Diagnosis Necrotizing enterocolitis | 31 Participants |
| Underlying Diagnosis Volvulus | 5 Participants |
| Weight (kg) at Treatment Start | 4.61 kg STANDARD_DEVIATION 2.09 |
| Weight Z Score at Treatment Start | -1.60 z-score STANDARD_DEVIATION 1.91 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 72 |
| other Total, other adverse events | 0 / 72 |
| serious Total, serious adverse events | 0 / 72 |
Outcome results
Primary
Number of Patients With Progression to Small Bowel Transplantation.
Whether or not the subject had an intestine-containing transplant or not
Time frame: Bi-weekly x4, then monthly until the completion of the study, for an overall average of 5.5 years follow-up for the cohort
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven™ | Number of Patients With Progression to Small Bowel Transplantation. | 19 Participants |
Secondary
Number of Subjects With Reversal of Biochemical Cholestasis
Of patients starting with elevated total serum bilirubin, the number that progress to normalization of serum total bilirubin in routine bloodwork
Time frame: weekly x 4, then bi-weekly x4, then monthly until the completion of the study, with an average follow-up of 5.5 years for the study cohort
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven™ | Number of Subjects With Reversal of Biochemical Cholestasis | 56 Participants |