Cholestasis
Conditions
Keywords
Parenteral Nutrition, Cholestasis
Brief summary
The purpose of this research study is to see if giving Omegaven (an intravenous fat emulsion containing fish oil) instead of the current lipid emulsion, which contains fat derived from soybeans, as part of your child's intravenous (IV) nutrition therapy may be tolerated better. It may reduce the harmful effects to the liver, may stop any further liver damage and may reverse damage already done to the liver because of the prolonged use of nutrition through your child's IV.
Detailed description
Enrollment of subjects into this study will occur for up to 4 years. Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require total parenteral nutrition or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids.
Interventions
DRUGOmegaven
For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Males and females ages one month of age to 18 years of age * Patients with intestinal failure on TPN * Patients who have a conjugated/direct bilirubin of ≥3 mg/dl for more than weeks and in whom other causes of cholestasis have been excluded with reasonable certainty utilizing biochemical, serologic, microbiologic, and radiographic techniques. Liver biopsy is not required to rule out other disorders, but may be utilized at the clinician's discretion * Patients in whom reduction of IV soy-based lipid to an average \<1.2g/kg body weight/day has failed to reduce the conjugated/direct bilirubin within ≥ 30 days of implementation * Willing to use birth control during study participation for females of child- bearing potential, as determined by investigator. * Signed informed consent for use of Omegaven® obtained
Exclusion criteria
* Any of the contraindications to use of Omegaven® * Impaired lipid metabolism (triglycerides \>1000 mg/dL) while on 1g/kg/day or less of Intralipid * History of severe hemorrhagic disorders (ie. hemophilia, Von Willebrand disease, etc.) * Unstable diabetes mellitus * Collapse and shock * Stroke/ Embolism * Cardiac infarction within the last 3 months * Undefined coma status * Pregnancy (positive pregnancy test) prior to enrollment in the study for females of child-bearing potential * Females of child-bearing potential who are unwilling to use birth control during study participation * Parental decision to forego the use of Omegaven® * Known fish or egg allergy * Pregnancy * Causes of liver disease other than Parenteral Nutrition Associated Cholestasis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in Conjugated/Direct Bilirubin | Completion of Therapy (time frame from 1-14 weeks) | Change in conjugated/direct bilirubin level to below 1 mg/dl. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in Unconjugated/Total Bilirubin | Completion of Therapy (time frame from 1-14 weeks) | Change in unconjugated/total bilirubin level to below 1.1 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes. |
| Number of Participants With a Change in Aspartate Transaminase (AST) | Completion of Therapy (time frame from 1-14 weeks) | Change in aspartate transaminase (AST) 57 units/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes. |
| Number of Participants With a Change in Liver Enzyme Gamma-glutamyltransferase (GGT) | Completion of Therapy (time frame from 1-14 weeks) | Change in Liver Enzyme Gamma-glutamyltransferase (GGT) to below 15 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes. |
| Number of Participants With a Change in Liver Enzyme Alkaline Phosphatase | Completion of Therapy (time frame from 1-14 weeks) | Change in liver enzyme alkaline phosphatase to below 345 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes. |
| Number of Participants With a Change in Triglycerides | Completion of Therapy (time frame from 1-14 weeks) | Change in Triglycerides to below 119 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes. |
| Number of Participants With a Change in Liver Enzyme (ALT) | Completion of Therapy (time frame from 1-14 weeks) | Change in liver enzyme ALT to below 59 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omegaven Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids.
Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Omegaven |
|---|---|
| Age, Continuous | 6 months |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 6 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
Number of Participants With a Change in Conjugated/Direct Bilirubin
Change in conjugated/direct bilirubin level to below 1 mg/dl.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Conjugated/Direct Bilirubin | 4 Participants |
Secondary
Number of Participants With a Change in Aspartate Transaminase (AST)
Change in aspartate transaminase (AST) 57 units/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Aspartate Transaminase (AST) | 2 Participants |
Secondary
Number of Participants With a Change in Liver Enzyme Alkaline Phosphatase
Change in liver enzyme alkaline phosphatase to below 345 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Liver Enzyme Alkaline Phosphatase | 3 Participants |
Secondary
Number of Participants With a Change in Liver Enzyme (ALT)
Change in liver enzyme ALT to below 59 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Liver Enzyme (ALT) | 1 Participants |
Secondary
Number of Participants With a Change in Liver Enzyme Gamma-glutamyltransferase (GGT)
Change in Liver Enzyme Gamma-glutamyltransferase (GGT) to below 15 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Liver Enzyme Gamma-glutamyltransferase (GGT) | 0 Participants |
Secondary
Number of Participants With a Change in Triglycerides
Change in Triglycerides to below 119 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Triglycerides | 8 Participants |
Secondary
Number of Participants With a Change in Unconjugated/Total Bilirubin
Change in unconjugated/total bilirubin level to below 1.1 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time frame: Completion of Therapy (time frame from 1-14 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven | Number of Participants With a Change in Unconjugated/Total Bilirubin | 5 Participants |