Parenteral Nutrition Associated Liver DiseasePhase 2/3ReversalNCT00910104
Cholestasis Reversal: Efficacy of IV Fish Oil
A Phase 2/3 study testing Omegaven® in people with Parenteral Nutrition Associated Liver Disease and Short Bowel Syndrome, run by Mark Puder at 1 site in United States.
Trial summary
The purpose of this study is to determine whether Omegaven is effective in the treatment of parenteral nutrition associated liver disease (PNALD). Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Parenteral Nutrition Associated Liver Disease, Short Bowel Syndrome, Gastrointestinal Disease
- 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
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to 23 Jan 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients will be PN dependent (unable to meet nutritional needs solely by enteral nutrition) and are expected to require PN for at least another 30 days
- Patients considered eligible for study participation must have parenteral nutrition associated liver disease (PNALD) as defined as a direct bilirubin of > 2 mg/dl or currently on Omegaven through another protocol. Other causes of liver disease should be excluded. A liver biopsy is not necessary for treatment.
- Direct bilirubin > 2.0 mg/dl or already on Omegaven through another protocol
- Signed patient informed consent.
- The patient must have utilized standard therapies to prevent the progression of his/her liver disease including surgical treatment, cyclic PN, avoiding overfeeding, reduction/removal of copper and manganese from PN, advancement of enteral feeding, and the use of ursodiol (i..e., Actigall®).
Who cannot join
- Pregnancy
- Other causes of chronic liver disease (Hepatitis C, biliary atresia, and alpha 1 anti-trypsin deficiency).
- Enrollment 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
- In rare instances, patients diagnosed with PNALD may later be found to have liver disease due to other causes in addition to the use of PN (i.e., inborn errors of metabolism, viral infections ). Such causes may not be known at the time of enrollment and will not preclude them from continuing in the study. For the sake of statistical analysis, however, these patients will be excluded although all data will be collected and reviewed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
The purpose of this study is to determine whether Omegaven is effective in the treatment of parenteral nutrition associated liver disease (PNALD).
Read the detailed description
The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven), when used in lieu of the conventional soy-based fat emulsion (Intralipid), is effective in the treatment of parenteral nutrition associated liver disease (PNALD).
- Conditions
- Parenteral Nutrition Associated Liver Disease, Short Bowel Syndrome, Gastrointestinal Disease
- Being tested
- Omegaven®
- Keywords
- PNALD, Omegaven, Parenteral Nutrition Associated Liver Disease, Cholestasis, Short Bowel Syndrome
- Medical subject headings
- Short Bowel Syndrome, Gastrointestinal Diseases, Cholestasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omegaven®Drug
Also called Fish Oil Lipid Emulsion (FOLE)
10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated
| Study group | Role | What they receive |
|---|---|---|
| Omegaven | Experimental | 1g/kg/day for duration of study participation for all participants Receives: Drug: Omegaven® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 2.0 mg/dL.
Time to reversal of established parenteral nutrition associated liver disease, defined as a decrease in direct bilirubin to <= 2.0 mg/dL.
Measured: Duration of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2009 (estimated)
- Study startAug 2006
- Primary completion23 Jan 2019
- Study completion23 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Parenteral Nutrition Associated Liver DiseaseStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Puder
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mark Puder, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00910104
- Sponsor's protocol ID
- 05-04-048
- Other IDs
- 1R01FD003460-02
- Acronym
- Reversal
- Status last verified
- Aug 2024
- First submitted
- 20 May 2009
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248.
PubMed 18310188Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. doi: 10.1542/peds.2005-2662.
PubMed 16818533Nandivada P, Anez-Bustillos L, O'Loughlin AA, Mitchell PD, Baker MA, Dao DT, Fell GL, Potemkin AK, Gura KM, Neufeld EJ, Puder M. Risk of post-procedural bleeding in children on intravenous fish oil. Am J Surg. 2017 Oct;214(4):733-737. doi: 10.1016/j.amjsurg.2016.10.026. Epub 2016 Dec 1.
PubMed 27979360Nandivada P, Baker MA, Mitchell PD, O'Loughlin AA, Potemkin AK, Anez-Bustillos L, Carlson SJ, Dao DT, Fell GL, Gura KM, Puder M. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr. 2016 Sep;104(3):663-70. doi: 10.3945/ajcn.116.137083. Epub 2016 Aug 10.
PubMed 27510535Nandivada P, Fell GL, Mitchell PD, Potemkin AK, O'Loughlin AA, Gura KM, Puder M. Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text]. JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):930-937. doi: 10.1177/0148607116633796. Epub 2016 Mar 9.
PubMed 26962059Nandivada P, Chang MI, Potemkin AK, Carlson SJ, Cowan E, O'loughlin AA, Mitchell PD, Gura KM, Puder M. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy. Ann Surg. 2015 Jan;261(1):172-9. doi: 10.1097/SLA.0000000000000445.
PubMed 24374535Le HD, de Meijer VE, Robinson EM, Zurakowski D, Potemkin AK, Arsenault DA, Fallon EM, Malkan A, Bistrian BR, Gura KM, Puder M. Parenteral fish-oil-based lipid emulsion improves fatty acid profiles and lipids in parenteral nutrition-dependent children. Am J Clin Nutr. 2011 Sep;94(3):749-58. doi: 10.3945/ajcn.110.008557. Epub 2011 Jul 20.
PubMed 21775562Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657.
PubMed 19661785Gura KM, Calkins KL, Premkumar MH, Puder M. Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events. J Pediatr. 2022 Feb;241:173-180.e1. doi: 10.1016/j.jpeds.2021.10.030. Epub 2021 Oct 23.
PubMed 34695449Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr. 2021 Mar;230:46-54.e2. doi: 10.1016/j.jpeds.2020.09.068. Epub 2020 Oct 8.
PubMed 33038344Gura K, Premkumar MH, Calkins KL, Puder M. Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease. J Pediatr. 2020 Apr;219:98-105.e4. doi: 10.1016/j.jpeds.2019.12.065. Epub 2020 Feb 12.
PubMed 32059815
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholestasis Reversal: Efficacy of IV Fish Oil
- ClinicalTrials.gov ID
- NCT00910104
- Acronym / sponsor ID
- Reversal / 05-04-048
- Conditions
- Parenteral Nutrition Associated Liver Disease, Short Bowel Syndrome, Gastrointestinal Disease
- Keywords
- PNALD, Omegaven, Parenteral Nutrition Associated Liver Disease, Cholestasis, Short Bowel Syndrome
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Mark PuderUniversity, hospital or other
- Study start
- Aug 2006 (actual)
- Primary completion
- 23 Jan 2019 (actual)
- Study completion
- 23 Jan 2019 (actual)
- First posted
- 29 May 2009 (estimated)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether Omegaven is effective in the treatment of parenteral nutrition associated liver disease (PNALD).
Detailed description
The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven), when used in lieu of the conventional soy-based fat emulsion (Intralipid), is effective in the treatment of parenteral nutrition associated liver disease (PNALD).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Omegaven | Experimental | Drug: Omegaven®1g/kg/day for duration of study participation for all participants |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Patients will be PN dependent (unable to meet nutritional needs solely by enteral nutrition) and are expected to require PN for at least another 30 days
- Patients considered eligible for study participation must have parenteral nutrition associated liver disease (PNALD) as defined as a direct bilirubin of > 2 mg/dl or currently on Omegaven through another protocol. Other causes of liver disease should be excluded. A liver biopsy is not necessary for treatment.
- Direct bilirubin > 2.0 mg/dl or already on Omegaven through another protocol
- Signed patient informed consent.
- The patient must have utilized standard therapies to prevent the progression of his/her liver disease including surgical treatment, cyclic PN, avoiding overfeeding, reduction/removal of copper and manganese from PN, advancement of enteral feeding, and the use of ursodiol (i..e., Actigall®).
Key exclusion criteria (5 listed)
- Pregnancy
- Other causes of chronic liver disease (Hepatitis C, biliary atresia, and alpha 1 anti-trypsin deficiency).
- Enrollment 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
- In rare instances, patients diagnosed with PNALD may later be found to have liver disease due to other causes in addition to the use of PN (i.e., inborn errors of metabolism, viral infections ). Such causes may not be known at the time of enrollment and will not preclude them from continuing in the study. For the sake of statistical analysis, however, these patients will be excluded although all data will be collected and reviewed.
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: Fish Oil Lipid Emulsion (FOLE)10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated | Drug | Omegaven |
Primary outcome
Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 2.0 mg/dL.
Time frame: Duration of treatment
Time to reversal of established parenteral nutrition associated liver disease, defined as a decrease in direct bilirubin to <= 2.0 mg/dL.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18310188Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248.
- Background: PubMed 16818533Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. doi: 10.1542/peds.2005-2662.
- Background: PubMed 27979360Nandivada P, Anez-Bustillos L, O'Loughlin AA, Mitchell PD, Baker MA, Dao DT, Fell GL, Potemkin AK, Gura KM, Neufeld EJ, Puder M. Risk of post-procedural bleeding in children on intravenous fish oil. Am J Surg. 2017 Oct;214(4):733-737. doi: 10.1016/j.amjsurg.2016.10.026. Epub 2016 Dec 1.
- Background: PubMed 27510535Nandivada P, Baker MA, Mitchell PD, O'Loughlin AA, Potemkin AK, Anez-Bustillos L, Carlson SJ, Dao DT, Fell GL, Gura KM, Puder M. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr. 2016 Sep;104(3):663-70. doi: 10.3945/ajcn.116.137083. Epub 2016 Aug 10.
- Background: PubMed 26962059Nandivada P, Fell GL, Mitchell PD, Potemkin AK, O'Loughlin AA, Gura KM, Puder M. Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text]. JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):930-937. doi: 10.1177/0148607116633796. Epub 2016 Mar 9.
- Background: PubMed 24374535Nandivada P, Chang MI, Potemkin AK, Carlson SJ, Cowan E, O'loughlin AA, Mitchell PD, Gura KM, Puder M. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy. Ann Surg. 2015 Jan;261(1):172-9. doi: 10.1097/SLA.0000000000000445.
- Background: PubMed 21775562Le HD, de Meijer VE, Robinson EM, Zurakowski D, Potemkin AK, Arsenault DA, Fallon EM, Malkan A, Bistrian BR, Gura KM, Puder M. Parenteral fish-oil-based lipid emulsion improves fatty acid profiles and lipids in parenteral nutrition-dependent children. Am J Clin Nutr. 2011 Sep;94(3):749-58. doi: 10.3945/ajcn.110.008557. Epub 2011 Jul 20.
- Results publication: PubMed 19661785Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657.
- Derived from this study: PubMed 34695449Gura KM, Calkins KL, Premkumar MH, Puder M. Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events. J Pediatr. 2022 Feb;241:173-180.e1. doi: 10.1016/j.jpeds.2021.10.030. Epub 2021 Oct 23.
- Derived from this study: PubMed 33038344Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr. 2021 Mar;230:46-54.e2. doi: 10.1016/j.jpeds.2020.09.068. Epub 2020 Oct 8.
- Derived from this study: PubMed 32059815Gura K, Premkumar MH, Calkins KL, Puder M. Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease. J Pediatr. 2020 Apr;219:98-105.e4. doi: 10.1016/j.jpeds.2019.12.065. Epub 2020 Feb 12.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Omegaven® in people with Parenteral Nutrition Associated Liver Disease and Short Bowel Syndrome, run by Mark Puder 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 5 inclusion and 5 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 19 Sep 2024. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 2.0 mg/dL. (time frame: Duration of treatment). 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 NCT00910104, which also lists 11 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 19 Sep 2024.