Liver InjuryNCT01089426
Omegaven Treatment of Parenteral Nutrition (PN) Induced Liver Injury
A study testing Omegaven™ in people with Liver Injury, run by Children's Hospital Los Angeles at 1 site in United States.
Trial summary
This study examines the hypothesis that administering intravenous fish oil, in lieu of intravenous soybean oil, can ameliorate the progression of PN-associated cholestatic liver disease in pediatric patients with elevated direct bilirubin requiring PN for more than 30 days. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Liver Injury
- What is being tested?
- Omegaven™
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Apr 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients will be parenteral nutrition dependent and are expected to require PN for at least another 30 days
- Patients must have parenteral nutrition associated liver disease (PNALD) as defined by having at least 2 consecutive direct bilirubins >2 mg/dl.
Who cannot join
- Pregnancy
- Other causes of liver disease
- Enrollment in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)
- Direct bilirubin < 2 mg/dl
- Allergy to any fish product, egg protein, and/or previous allergy to Omegaven
- Active coagulopathy characterized by on-going bleeding or acute need for clotting factor replacement such as FFP or cryoprecipitate to maintain homeostasis
Show all 14Show fewer
- Impaired lipid metabolism as defined by serum Tg level >400 at time of initiation of Omegaven
- Unstable diabetes mellitus
- Recent stroke/embolism, not including catheter related thrombosis, which is a common complication of central venous catheter.
- Collapse and shock
- Undefined coma status
- Untreated infection at time of initiation of Omegaven
- Hemodynamic instability
- > 21 years of age
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens Hospital Los Angeles
Los Angeles, California, 90027-6016
About this study
Official title: Research Study of an Intravenous Fat Emulsion Comprised of Fish Oils (Omegaven) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury
This study examines the hypothesis that administering intravenous fish oil, in lieu of intravenous soybean oil, can ameliorate the progression of PN-associated cholestatic liver disease in pediatric patients with elevated direct bilirubin requiring PN for more than 30 days.
Read the detailed description
In the United States, patients dependent upon parenteral nutrition (PN) receive parenteral fat emulsions composed of soybean oils. Lipids are necessary in PN dependent patients due to their high caloric value and essential fatty acid content. They have been implicated in predisposing patients to PN associated liver disease. Phytosterols such as those contained in soybean oils are thought to have a deleterious effect on biliary secretion.
Children requiring prolonged PN are at risk for developing PN associated liver disease. We hypothesize that although omega-6 fatty acid emulsions prevent fatty acid deficiency, they are not cleared in a manner similar to enteral chylomicrons and therefore accumulate in the liver and resulting in steatotic liver injury. We further hypothesize that a fat emulsion comprised of omega-3 fatty acids (i.e., fish oil) such as Omegaven™ would be beneficial in the management of steatotic liver injury by its inhibition of de novo lipogenesis, the reduction of arachidonic acid-derived inflammatory mediators, prevention of essential fatty acid deficiency through the presence of small amounts of arachidonic acid, and improved clearance of lipids from the serum. Animal studies have shown that IV fat emulsions (IFE) such as fish oil that are high in eicosapentaenic and docashexaaenoic acid reduce impairment of bile flow which is seen in cholestasis caused by conventional fat emulsions. Intravenous omega three fatty acids may be well tolerated and might reduce the inflammatory effect in the liver of prolonged PN exposure and could potentially reverse any hepatic dysfunction due to PN/IFE use. By administering Omegaven™ in place of conventional phytosterol/soybean fat emulsions we may reverse or prevent the progression of PN associated cholestasis and thus allow the patient to be maintained on adequate PN until they are able to ingest adequate nutrition enterally.
- Conditions
- Liver Injury
- Being tested
- Omegaven™, Historical Controls
- Keywords
- Pediatric patients with Parenteral Nutrition (PN) induced Liver Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omegaven™Drug
Also called Highly refined fish oil for intravenous administration (10% Omegaven™)
1 g/kg/d of Omegaven until discontinuation of PN
Historical ControlsOther
Standard of Care
| Study group | Role | What they receive |
|---|---|---|
| Historical controls | Other | A subset of patients previously seen, who have had at least 2 consecutive direct bilirubin levels > 2 mg/dL, who depended on parenteral nutrition for at least 90 days after surgical therapy for congenital or acquired intestinal diseases Receives: Other: Historical Controls |
| Omegaven™ | Experimental | Not described Receives: Drug: Omegaven™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of reduction of direct bilirubin
Measured: normalization of direct bilirubin: an expected average of approximately 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2010 (estimated)
- Study startSep 2008
- Primary completionApr 2019
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Liver InjuryStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Russell Merritt, Children's Hospital Los Angeles
- Investigators
- Russell Merritt, M.D., PhD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01089426
- Sponsor's protocol ID
- CCI-08-00127
- Status last verified
- May 2019
- First submitted
- 15 Mar 2010
- Last updated
- 6 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term total parenteral nutrition with growth, development, and positive nitrogen balance. Surgery. 1968 Jul;64(1):134-42. No abstract available.
PubMed 4968812Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA. 1968 Mar 4;203(10):860-4. No abstract available.
PubMed 4965871Mullick FG, Moran CA, Ishak KG. Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. Mod Pathol. 1994 Feb;7(2):190-4.
PubMed 8008742Freund HR. Abnormalities of liver function and hepatic damage associated with total parenteral nutrition. Nutrition. 1991 Jan-Feb;7(1):1-5; discussion 5-6.
PubMed 1802177Beath SV, Davies P, Papadopoulou A, Khan AR, Buick RG, Corkery JJ, Gornall P, Booth IW. Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors. J Pediatr Surg. 1996 Apr;31(4):604-6. doi: 10.1016/s0022-3468(96)90507-2.
PubMed 8801324Greenberg GR, Wolman SL, Christofides ND, Bloom SR, Jeejeebhoy KN. Effect of total parenteral nutrition on gut hormone release in humans. Gastroenterology. 1981 May;80(5 pt 1):988-93. No abstract available.
PubMed 6781979Yeh SL, Chen WJ, Huang PC. Effects of L-glutamine on induced hepatosteatosis in rats receiving total parenteral nutrition. J Formos Med Assoc. 1995 Oct;94(10):593-9.
PubMed 8527958Kubota A, Yonekura T, Hoki M, Oyanagi H, Kawahara H, Yagi M, Imura K, Iiboshi Y, Wasa K, Kamata S, Okada A. Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience. J Pediatr Surg. 2000 Jul;35(7):1049-51. doi: 10.1053/jpsu.2000.7769.
PubMed 10917294Moss RL, Das JB, Ansari G, Raffensperger JG. Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration. J Pediatr Surg. 1993 Mar;28(3):391-6; discussion 396-7. doi: 10.1016/0022-3468(93)90238-g.
PubMed 8468653Helms RA, Christensen ML, Mauer EC, Storm MC. Comparison of a pediatric versus standard amino acid formulation in preterm neonates requiring parenteral nutrition. J Pediatr. 1987 Mar;110(3):466-70. doi: 10.1016/s0022-3476(87)80519-x. No abstract available.
PubMed 3102712Moss RL, Haynes AL, Pastuszyn A, Glew RH. Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. Pediatr Res. 1999 May;45(5 Pt 1):664-8. doi: 10.1203/00006450-199905010-00009.
PubMed 10231861Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome. J Pediatr Surg. 1997 Mar;32(3):473-5. doi: 10.1016/s0022-3468(97)90609-6.
PubMed 9094021Whalen GF, Shamberger RC, Perez-Atayde A, Folkman J. A proposed cause for the hepatic dysfunction associated with parenteral nutrition. J Pediatr Surg. 1990 Jun;25(6):622-6. doi: 10.1016/0022-3468(90)90348-d.
PubMed 2113578Zamir O, Nussbaum MS, Bhadra S, Subbiah MT, Rafferty JF, Fischer JE. Effect of enteral feeding on hepatic steatosis induced by total parenteral nutrition. JPEN J Parenter Enteral Nutr. 1994 Jan-Feb;18(1):20-5. doi: 10.1177/014860719401800120.
PubMed 8164298Kaminski DL, Adams A, Jellinek M. The effect of hyperalimentation on hepatic lipid content and lipogenic enzyme activity in rats and man. Surgery. 1980 Jul;88(1):93-100. No abstract available.
PubMed 6104363
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Research Study of an Intravenous Fat Emulsion Comprised of Fish Oils (Omegaven) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury
- ClinicalTrials.gov ID
- NCT01089426
- Acronym / sponsor ID
- CCI-08-00127
- Conditions
- Liver Injury
- Keywords
- Pediatric patients with Parenteral Nutrition (PN) induced Liver Injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Apr 2019 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 18 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study examines the hypothesis that administering intravenous fish oil, in lieu of intravenous soybean oil, can ameliorate the progression of PN-associated cholestatic liver disease in pediatric patients with elevated direct bilirubin requiring PN for more than 30 days.
Detailed description
In the United States, patients dependent upon parenteral nutrition (PN) receive parenteral fat emulsions composed of soybean oils. Lipids are necessary in PN dependent patients due to their high caloric value and essential fatty acid content. They have been implicated in predisposing patients to PN associated liver disease. Phytosterols such as those contained in soybean oils are thought to have a deleterious effect on biliary secretion.
Children requiring prolonged PN are at risk for developing PN associated liver disease. We hypothesize that although omega-6 fatty acid emulsions prevent fatty acid deficiency, they are not cleared in a manner similar to enteral chylomicrons and therefore accumulate in the liver and resulting in steatotic liver injury. We further hypothesize that a fat emulsion comprised of omega-3 fatty acids (i.e., fish oil) such as Omegaven™ would be beneficial in the management of steatotic liver injury by its inhibition of de novo lipogenesis, the reduction of arachidonic acid-derived inflammatory mediators, prevention of essential fatty acid deficiency through the presence of small amounts of arachidonic acid, and improved clearance of lipids from the serum. Animal studies have shown that IV fat emulsions (IFE) such as fish oil that are high in eicosapentaenic and docashexaaenoic acid reduce impairment of bile flow which is seen in cholestasis caused by conventional fat emulsions. Intravenous omega three fatty acids may be well tolerated and might reduce the inflammatory effect in the liver of prolonged PN exposure and could potentially reverse any hepatic dysfunction due to PN/IFE use. By administering Omegaven™ in place of conventional phytosterol/soybean fat emulsions we may reverse or prevent the progression of PN associated cholestasis and thus allow the patient to be maintained on adequate PN until they are able to ingest adequate nutrition enterally.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Historical controls | Other | Other: Historical ControlsA subset of patients previously seen, who have had at least 2 consecutive direct bilirubin levels > 2 mg/dL, who depended on parenteral nutrition for at least 90 days after surgical therapy for congenital or acquired intestinal diseases |
| Omegaven™ | Experimental | Drug: Omegaven™ |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Patients will be parenteral nutrition dependent and are expected to require PN for at least another 30 days
- Patients must have parenteral nutrition associated liver disease (PNALD) as defined by having at least 2 consecutive direct bilirubins >2 mg/dl.
Key exclusion criteria (14 listed)
- Pregnancy
- Other causes of liver disease
- Enrollment in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team)
- Direct bilirubin < 2 mg/dl
- Allergy to any fish product, egg protein, and/or previous allergy to Omegaven
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omegaven™Also: Highly refined fish oil for intravenous administration (10% Omegaven™)1 g/kg/d of Omegaven until discontinuation of PN | Drug | Omegaven™ |
| Historical ControlsStandard of Care | Other | Historical controls |
Primary outcome
Rate of reduction of direct bilirubin
Time frame: normalization of direct bilirubin: an expected average of approximately 5 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2019.
- Background: PubMed 4968812Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term total parenteral nutrition with growth, development, and positive nitrogen balance. Surgery. 1968 Jul;64(1):134-42. No abstract available.
- Background: PubMed 4965871Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA. 1968 Mar 4;203(10):860-4. No abstract available.
- Background: PubMed 8008742Mullick FG, Moran CA, Ishak KG. Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. Mod Pathol. 1994 Feb;7(2):190-4.
- Background: PubMed 1802177Freund HR. Abnormalities of liver function and hepatic damage associated with total parenteral nutrition. Nutrition. 1991 Jan-Feb;7(1):1-5; discussion 5-6.
- Background: PubMed 8801324Beath SV, Davies P, Papadopoulou A, Khan AR, Buick RG, Corkery JJ, Gornall P, Booth IW. Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors. J Pediatr Surg. 1996 Apr;31(4):604-6. doi: 10.1016/s0022-3468(96)90507-2.
- Background: PubMed 6781979Greenberg GR, Wolman SL, Christofides ND, Bloom SR, Jeejeebhoy KN. Effect of total parenteral nutrition on gut hormone release in humans. Gastroenterology. 1981 May;80(5 pt 1):988-93. No abstract available.
- Background: PubMed 8527958Yeh SL, Chen WJ, Huang PC. Effects of L-glutamine on induced hepatosteatosis in rats receiving total parenteral nutrition. J Formos Med Assoc. 1995 Oct;94(10):593-9.
- Background: PubMed 10917294Kubota A, Yonekura T, Hoki M, Oyanagi H, Kawahara H, Yagi M, Imura K, Iiboshi Y, Wasa K, Kamata S, Okada A. Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience. J Pediatr Surg. 2000 Jul;35(7):1049-51. doi: 10.1053/jpsu.2000.7769.
- Background: PubMed 8468653Moss RL, Das JB, Ansari G, Raffensperger JG. Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration. J Pediatr Surg. 1993 Mar;28(3):391-6; discussion 396-7. doi: 10.1016/0022-3468(93)90238-g.
- Background: PubMed 3102712Helms RA, Christensen ML, Mauer EC, Storm MC. Comparison of a pediatric versus standard amino acid formulation in preterm neonates requiring parenteral nutrition. J Pediatr. 1987 Mar;110(3):466-70. doi: 10.1016/s0022-3476(87)80519-x. No abstract available.
- Background: PubMed 10231861Moss RL, Haynes AL, Pastuszyn A, Glew RH. Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. Pediatr Res. 1999 May;45(5 Pt 1):664-8. doi: 10.1203/00006450-199905010-00009.
- Background: PubMed 9094021Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome. J Pediatr Surg. 1997 Mar;32(3):473-5. doi: 10.1016/s0022-3468(97)90609-6.
Related trials for Liver Injury
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
Recruiting
Avoiding Recooling After Normothermic Machine Perfusion in Liver Transplantation
Liver Transplantation (LT), Ischemia-Reperfusion Injury
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Russell Merritt, M.D., PhD principal investigator
Children's Hospital Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Omegaven™ in people with Liver Injury, run by Children's Hospital Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of reduction of direct bilirubin (time frame: normalization of direct bilirubin: an expected average of approximately 5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01089426, which also lists 30 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2019.