CholestasisPhase 2FONCT00969332
A Safety and Efficacy Study to Determine if Giving Intravenous Fish Oil Helps Children With Liver Disease
A Phase 2 study testing Omegaven in people with Cholestasis, run by University of California, Los Angeles at 1 site in United States.
Trial summary
The purpose of the study is to investigate if intravenous fish oil, commercially available as Omegaven, safely and effectively reverses parenteral nutrition associated cholestasis in children. Read more about this study
- Who is it for?
- Ages 2 weeks to 18 years
- Conditions the study is for
- Cholestasis
- 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
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to 12 Feb 2019
- Phase
- Phase 2
- 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 2 weeks to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Clinical evidence of parenteral nutrition associated cholestasis
- Direct bilirubin greater or equal to 2 mg/dL on 2 consecutive measurements
- Expected parenteral nutrition course greater than 30 days
- Acquired or congenital gastrointestinal disease
- > 2 weeks of age and < 18 years of age
- > 60% calories from parenteral nutrition
- Failed standard therapies to prevent progression of liver disease (Actigal, cyclic parenteral nutrition, avoidance of overfeeding, reduction/removal of copper from parenteral nutrition if elevated my laboratory analysis, advancement of enteral feeds)
Who cannot join
- Inborn errors of metabolism
- Extracorporeal Membrane Oxygenation
- Seafood, egg, or Omegaven allergy
- Documented case of liver disease other than Parenteral Nutrition Associated Cholestasis
- Hemorrhagic disorder
- Anticoagulant therapy
Show all 17Show fewer
- Hemodynamically unstable or in shock
- Comatose state
- Stroke, pulmonary embolism, recent myocardial infarction
- Diabetes
- Fatal chromosomal disorder
- Enrollment in any other clinical trial involving an investigational agent
- Patient, parent, or legal guardians unable or unwilling to give consent
- Patient expected to be weaned from parenteral nutrition in 30 days
- unable to tolerate necessary monitoring
- Patient requiring aspirin or toradel or motrin
- Patient requiring dialysis
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095
About this study
Official title: Omegaven and Parenteral Nutrition Associated Cholestasis
The purpose of the study is to investigate if intravenous fish oil, commercially available as Omegaven, safely and effectively reverses parenteral nutrition associated cholestasis in children.
Read the detailed description
Infants dependent on parenteral nutrition for greater than 1 year who develop parenteral nutrition associated cholestasis will universally face mortality unless they receive a timely liver and/or small bowel transplant. Although transplant survival has improved in recent years, survival is not guaranteed, and transplant care remains costly. Alternative nutritional and pharmacological strategies are imperative to improve the clinical outcomes of infants with intestinal failure and parenteral nutrition associated cholestasis. In both animal and human studies, intravenous fish oil, a lipid emulsion rich in omega-3 fatty acids and Vitamin E, and lacking phytosterols, has been shown to ameliorate parenteral nutrition associated cholestasis and improve morbidity and mortality. The purpose of this pilot study is to investigate if Omegaven, a commercially available intravenous fish oil, at 1 g/kg/d, will safely reverse liver disease in 80 subjects with parenteral nutrition associated cholestasis. Subjects can initially receive a maximum of 6 months (24 weeks) of intravenous fish oil. If the subject re-develops liver disease and still satisfies inclusion/exclusion criteria, the intervention can be restarted. Study subjects will be compared to a historical cohort of children with Short Bowel Syndrome and parenteral nutrition associated cholestasis who have been receiving standard intravenous soybean oil for > 60 days. The fish oil cohort will be followed for a total of 5 years to determine if transplant-free mortality is reduced.
- Conditions
- Cholestasis
- Being tested
- Omegaven
- Keywords
- liver, parenteral nutrition, fish oil, omegaven, children
- Medical subject headings
- Cholestasis, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmegavenDrug
0.5 g/kg/d intravenous every day for 2 days, then 1 g/kg/d intravenous everyday
| Study group | Role | What they receive |
|---|---|---|
| Omegaven | Experimental | 0.5 g/kg/d IV x 2 days, then 1 g/kg/d IV for 24 weeks or until parenteral nutrition discontinuation, death or transplant, whichever comes first. Subjects are eligible to restart Omegaven should they re-satisfy inclusion/exclusion criteria. Receives: Drug: Omegaven |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Reversal of Parenteral Nutrition Associated Cholestasis
weeks
Measured: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Secondary outcomes (10)
Death
expiration
Measured: 24 weeks, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Number of Participants Who Underwent a Transplant
includes isolated liver or multi-visceral transplant including liver graft
Measured: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Time to Full Enteral Feeds
discontinuation of parenteral nutrition
Measured: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Growth Z-scores
Weight Z-scores at the end of the study. Formula used: (weight at end of study-average weight of reference population)/standard deviation of weight of reference population.
The Z-score indicates the number of standard deviations away from the mean. A weight Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A weight Z-score </= -2 indicates an underweight or malnourished status, while a weight Z-score >/= 2 indicates an overweight or obese status.
Measured: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Platelet Counts at the End of the Study - Risk of Bleeding
platelet counts at the end of the study
Measured: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Number of Participants With Essential Fatty Acid Deficiency
triene:tetraene ratio less than 0.2
Measured: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Inflammation
Serum Cytokines - interleukin-8
Measured: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Sterol Metabolism
Serum Phytosterols - stigmasterol
Measured: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Bile Acid Metabolism
Serum Bile acids - total chenodeoxycholic acid
Measured: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Fatty Acid Metabolism
Erythrocyte fatty acid - Docosahexaenoic Acid
Measured: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2009 (estimated)
- Study startAug 2009
- Primary completion12 Jan 2019
- Study completion12 Feb 2019
Why it stopped: study intervention was approved by the FDA
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 (5)Papers the sponsor has linked to this study.
- Other trials for CholestasisStudies of the same condition, open and under way.
- More trials run by University of California, 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kara L. Calkins, MD, University of California, Los Angeles
- Investigators
- Kara L Calkins, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00969332
- Sponsor's protocol ID
- 09-02-079-02
- Acronym
- FO
- Status last verified
- Feb 2020
- First submitted
- 31 Aug 2009
- Last updated
- 26 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Calkins KL, Dunn JC, Shew SB, Reyen L, Farmer DG, Devaskar SU, Venick RS. Pediatric intestinal failure-associated liver disease is reversed with 6 months of intravenous fish oil. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):682-92. doi: 10.1177/0148607113495416. Epub 2013 Jul 26.
PubMed 23894176Calkins KL, DeBarber A, Steiner RD, Flores MJ, Grogan TR, Henning SM, Reyen L, Venick RS. Intravenous Fish Oil and Pediatric Intestinal Failure-Associated Liver Disease: Changes in Plasma Phytosterols, Cytokines, and Bile Acids and Erythrocyte Fatty Acids. JPEN J Parenter Enteral Nutr. 2018 Mar;42(3):633-641. doi: 10.1177/0148607117709196. Epub 2017 Dec 18.
PubMed 28521607Wang C, Venick RS, Shew SB, Dunn JCY, Reyen L, Gou R, Calkins KL. Long-Term Outcomes in Children With Intestinal Failure-Associated Liver Disease Treated With 6 Months of Intravenous Fish Oil Followed by Resumption of Intravenous Soybean Oil. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):708-716. doi: 10.1002/jpen.1463. Epub 2018 Nov 8.
PubMed 30411372Ong ML, Venick RS, Shew SB, Dunn JCY, Reyen L, Grogan T, Calkins KL. Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):717-725. doi: 10.1002/jpen.1532. Epub 2019 Mar 22.
PubMed 30900274Calkins KL, Thamotharan S, Ghosh S, Dai Y, Devaskar SU. MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil. J Nutr. 2020 May 1;150(5):1144-1150. doi: 10.1093/jn/nxaa001.
PubMed 32072161
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Omegaven and Parenteral Nutrition Associated Cholestasis
- ClinicalTrials.gov ID
- NCT00969332
- Acronym / sponsor ID
- FO / 09-02-079-02
- Conditions
- Cholestasis
- Keywords
- liver, parenteral nutrition, fish oil, omegaven, children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study intervention was approved by the FDA
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Aug 2009 (actual)
- Primary completion
- 12 Jan 2019 (actual)
- Study completion
- 12 Feb 2019 (actual)
- First posted
- 1 Sep 2009 (estimated)
- Results
- Posted 12 Feb 2020
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 the study is to investigate if intravenous fish oil, commercially available as Omegaven, safely and effectively reverses parenteral nutrition associated cholestasis in children.
Detailed description
Infants dependent on parenteral nutrition for greater than 1 year who develop parenteral nutrition associated cholestasis will universally face mortality unless they receive a timely liver and/or small bowel transplant. Although transplant survival has improved in recent years, survival is not guaranteed, and transplant care remains costly. Alternative nutritional and pharmacological strategies are imperative to improve the clinical outcomes of infants with intestinal failure and parenteral nutrition associated cholestasis. In both animal and human studies, intravenous fish oil, a lipid emulsion rich in omega-3 fatty acids and Vitamin E, and lacking phytosterols, has been shown to ameliorate parenteral nutrition associated cholestasis and improve morbidity and mortality. The purpose of this pilot study is to investigate if Omegaven, a commercially available intravenous fish oil, at 1 g/kg/d, will safely reverse liver disease in 80 subjects with parenteral nutrition associated cholestasis. Subjects can initially receive a maximum of 6 months (24 weeks) of intravenous fish oil. If the subject re-develops liver disease and still satisfies inclusion/exclusion criteria, the intervention can be restarted. Study subjects will be compared to a historical cohort of children with Short Bowel Syndrome and parenteral nutrition associated cholestasis who have been receiving standard intravenous soybean oil for > 60 days. The fish oil cohort will be followed for a total of 5 years to determine if transplant-free mortality is reduced.
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: Omegaven0.5 g/kg/d IV x 2 days, then 1 g/kg/d IV for 24 weeks or until parenteral nutrition discontinuation, death or transplant, whichever comes first. Subjects are eligible to restart Omegaven should they re-satisfy inclusion/exclusion criteria. |
Who may qualify
- Ages
- 2 weeks to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Clinical evidence of parenteral nutrition associated cholestasis
- Direct bilirubin greater or equal to 2 mg/dL on 2 consecutive measurements
- Expected parenteral nutrition course greater than 30 days
- Acquired or congenital gastrointestinal disease
- > 2 weeks of age and < 18 years of age
Key exclusion criteria (17 listed)
- Inborn errors of metabolism
- Extracorporeal Membrane Oxygenation
- Seafood, egg, or Omegaven allergy
- Documented case of liver disease other than Parenteral Nutrition Associated Cholestasis
- Hemorrhagic disorder
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 |
|---|---|---|
| Omegaven0.5 g/kg/d intravenous every day for 2 days, then 1 g/kg/d intravenous everyday | Drug | Omegaven |
Primary outcome
Time to Reversal of Parenteral Nutrition Associated Cholestasis
Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
weeks
10 secondary outcomes
Death
Time frame: 24 weeks, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Number of Participants Who Underwent a Transplant
Time frame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Time to Full Enteral Feeds
Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Growth Z-scores
Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Platelet Counts at the End of the Study - Risk of Bleeding
Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Number of Participants With Essential Fatty Acid Deficiency
Time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Inflammation
Time frame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Sterol Metabolism
Time frame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Bile Acid Metabolism
Time frame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Markers of Fatty Acid Metabolism
Time frame: 24 weeks, death, or discontinuation of Parenteral Nutrition (whichever comes first)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23894176Calkins KL, Dunn JC, Shew SB, Reyen L, Farmer DG, Devaskar SU, Venick RS. Pediatric intestinal failure-associated liver disease is reversed with 6 months of intravenous fish oil. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):682-92. doi: 10.1177/0148607113495416. Epub 2013 Jul 26.
- Results publication: PubMed 28521607Calkins KL, DeBarber A, Steiner RD, Flores MJ, Grogan TR, Henning SM, Reyen L, Venick RS. Intravenous Fish Oil and Pediatric Intestinal Failure-Associated Liver Disease: Changes in Plasma Phytosterols, Cytokines, and Bile Acids and Erythrocyte Fatty Acids. JPEN J Parenter Enteral Nutr. 2018 Mar;42(3):633-641. doi: 10.1177/0148607117709196. Epub 2017 Dec 18.
- Results publication: PubMed 30411372Wang C, Venick RS, Shew SB, Dunn JCY, Reyen L, Gou R, Calkins KL. Long-Term Outcomes in Children With Intestinal Failure-Associated Liver Disease Treated With 6 Months of Intravenous Fish Oil Followed by Resumption of Intravenous Soybean Oil. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):708-716. doi: 10.1002/jpen.1463. Epub 2018 Nov 8.
- Results publication: PubMed 30900274Ong ML, Venick RS, Shew SB, Dunn JCY, Reyen L, Grogan T, Calkins KL. Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):717-725. doi: 10.1002/jpen.1532. Epub 2019 Mar 22.
- Derived from this study: PubMed 32072161Calkins KL, Thamotharan S, Ghosh S, Dai Y, Devaskar SU. MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil. J Nutr. 2020 May 1;150(5):1144-1150. doi: 10.1093/jn/nxaa001.
- Individual participant dataSharing planned: No
Related trials for Cholestasis
Active, not recruitingPhase 3
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cirrhosis
RecruitingPhase 3
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
Primary Biliary Cholangitis
RecruitingPhase 3
FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy
Primary Biliary Cholangitis (PBC)
RecruitingPhase 3
Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid
Primary Biliary Cirrhosis
RecruitingPhase 2/3
Fenofibrate in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis
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.
Kara L Calkins, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omegaven in people with Cholestasis, run by University of California, 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 7 inclusion and 17 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: stopped early, as of the sponsor's last update on 26 Feb 2020. 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 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.
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 12 Feb 2020). 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?
Time to Reversal of Parenteral Nutrition Associated Cholestasis (time frame: 24 weeks, death, transplant, or discontinuation of Parenteral Nutrition (whichever comes first)). 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 NCT00969332, which also lists 5 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 26 Feb 2020.