Total Parenteral Nutrition-induced Cholestasis
Conditions
Keywords
PNALD, Cholestasis, Omegaven®, Short Bowel Syndrome
Brief summary
The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven®), when used in place of the conventional soy-based fat emulsion (Intralipid), is effective in treating parenteral nutrition associated liver disease (PNALD) in children. The study hypothesis is that Omegaven® can be safely provided to children who are dependent on parenteral nutrition and have PNALD, and can reverse or prevent progression of PNALD until the child can take adequate nutrition by mouth.
Detailed description
Rationale for Omegaven® Treatment Unlike conventional intravenous fat emulsions, Omegaven® is comprised solely of fish oils containing primarily omega-3 fatty acids. Animal studies have shown that IV lipid emulsions such as fish oil that are high in eicosapentaenic and docosahexaenoic acid reduce impairment of bile flow as seen in cholestasis caused by conventional fat emulsions(1,2). By administering Omegaven® in place of conventional phytosterol/soybean fat emulsions, the cholestasis may be reversed and patients will be able to be maintained on adequate PN until they are able to ingest adequate nutrition enterally. References 1. Chen W. Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:24. 2. Yeh S. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:80.
Interventions
DRUGOmegaven®
10% Omegaven® initiated at a starting dose of 0.5g/kg/day for two days and then advancing to the goal dose of 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 18 Years
Healthy volunteers
No
Inclusion criteria
* Children 0-18 years of age * Patients will be PN-dependent and expected to continue PN for at least 30 days * Patients considered eligible for study participation must have PN-associated liver diseases . Other causes of liver disease (i.e., biliary atresia, galactosemia, alpha-1 antitrypsin deficiency) will be excluded. A liver biopsy is not necessary for treatment * Direct bilirubin \> 2.0 mg/dl * Signed patient informed consent * Signed patient assent where applicable.
Exclusion criteria
* Pregnancy * Other causes of chronic liver disease (cystic fibrosis, biliary atresia, alpha-1 antitrypsin deficiency) * Signs of advanced liver disease including cirrhosis on biopsy, varices, ascites * The patient is allergic to eggs/shellfish * The patient has a severe hemorrhagic disorder * The patient is enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team) * The parent or guardian or child unwilling to provide consent or assent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Normalization of Direct Bilirubin | Month 9 | Normalization of direct bilirubin is defined as less than 0.4mg/dL by 9 months. This relates to the efficacy of parenteral administration of fish oil derived fat emulsion (Omegaven®) to reverse established parenteral nutrition associated liver disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Normal Essential Fatty Acid (EFA) Profiles. | Months 1 through 9 | EFA is defined at a triene tetraene ratio of greater than 0.2 (so normal is \> 0.2). Collected monthly from month 1-9. |
| Number of Participants With Triglyceride Levels > 400 mg/dL | baseline data and then weekly and monthly evaluations, for an average of 9 months | Number of participants with triglyceride levels \> 400 mg/dL |
| Number of Participants With Unexpected Bleeding or Coagulopathies | Month 6 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Single Omegaven® Intervention Arm
Omegaven®: 10% Omegaven® initiated at a starting dose of 0.5g/kg/day for two days and then advancing to the goal dose of 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 11 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Number of Participants With Normalization of Direct Bilirubin
Normalization of direct bilirubin is defined as less than 0.4mg/dL by 9 months. This relates to the efficacy of parenteral administration of fish oil derived fat emulsion (Omegaven®) to reverse established parenteral nutrition associated liver disease.
Time frame: Month 9
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm | Number of Participants With Normalization of Direct Bilirubin | 11 participants |
Secondary
Number of Participants With Normal Essential Fatty Acid (EFA) Profiles.
EFA is defined at a triene tetraene ratio of greater than 0.2 (so normal is \> 0.2). Collected monthly from month 1-9.
Time frame: Months 1 through 9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm | Number of Participants With Normal Essential Fatty Acid (EFA) Profiles. | 10 Participants |
Secondary
Number of Participants With Triglyceride Levels > 400 mg/dL
Number of participants with triglyceride levels \> 400 mg/dL
Time frame: baseline data and then weekly and monthly evaluations, for an average of 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm | Number of Participants With Triglyceride Levels > 400 mg/dL | 0 Participants |
Secondary
Number of Participants With Unexpected Bleeding or Coagulopathies
Time frame: Month 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm | Number of Participants With Unexpected Bleeding or Coagulopathies | 0 Participants |