Total Parenteral Nutrition-induced CholestasisPhase 2NCT01845116

Omegaven® in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

A Phase 2 study testing Omegaven® in people with Total Parenteral Nutrition-induced Cholestasis, run by Wake Forest University Health Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 4 weeks to 18 years
Conditions the study is for: Total Parenteral Nutrition-induced 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: 11 participants
Where: 1 siteUnited States
Study dates: Jul 2010to Jul 2020
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 4 weeks to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Levine Children's Hospital at Carolinas HealthCare System
Charlotte, North Carolina, 28232-2861

Other trials in United States

About this study

Official title: Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury

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.

Read the 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

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.
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.

Conditions: Total Parenteral Nutrition-induced Cholestasis
Being tested: Omegaven®
Keywords: PNALD, Cholestasis, Omegaven®, Short Bowel Syndrome
Medical subject headings: Cholestasis, Short Bowel Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Omegaven®Drug
Also called IV Fish Oil Based Lipid Emulsion
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.

Study groups in NCT01845116
Study group	Role	What they receive
Single Arm	Other	Single Omegaven® Intervention Arm Receives: Drug: Omegaven®

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Month 9

Secondary outcomes (3)

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.
Measured: Months 1 through 9
Number of Participants With Triglyceride Levels > 400 mg/dL
Number of participants with triglyceride levels > 400 mg/dL
Measured: baseline data and then weekly and monthly evaluations, for an average of 9 months
Number of Participants With Unexpected Bleeding or Coagulopathies
Measured: Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2010Jul 2020

First posted3 May 2013 (estimated)
Study startJul 2010
Primary completionJul 2020
Study completionJul 2020

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 (3)Papers the sponsor has linked to this study.
Other trials for Total Parenteral Nutrition-induced CholestasisStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe 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: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01845116
Sponsor's protocol ID: Omegaven 04-10-18B
Status last verified: Sep 2022
First submitted: 29 Apr 2013
Last updated: 23 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Upon study completion

Publications

Puder 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 19661785
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 18310188
Gura 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 16818533

Study at a glance

From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment of Parenteral Nutrition (PN) Induced Liver Injury
ClinicalTrials.gov ID: NCT01845116
Acronym / sponsor ID: Omegaven 04-10-18B
Conditions: Total Parenteral Nutrition-induced Cholestasis
Keywords: PNALD, Cholestasis, Omegaven®, Short Bowel Syndrome
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Study start: Jul 2010 (actual)
Primary completion: Jul 2020 (actual)
Study completion: Jul 2020 (actual)
First posted: 3 May 2013 (estimated)
Results: Posted 23 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Rationale for Omegaven® Treatment

References

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.
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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Single Arm	Other	Drug: Omegaven®Single Omegaven® Intervention Arm

Who may qualify

Ages: 4 weeks to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (7 listed)

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

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: IV Fish Oil Based Lipid Emulsion10% 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.	Drug	Single Arm

Primary outcome

Number of Participants With Normalization of Direct Bilirubin
Time frame: 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.

3 secondary outcomes

Number of Participants With Normal Essential Fatty Acid (EFA) Profiles.
Time frame: Months 1 through 9
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
Number of Participants With Unexpected Bleeding or Coagulopathies
Time frame: Month 6

Results and safety

Results posted to the registry on 23 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Single Arm	11	11

Primary outcome: Number of Participants With Normalization of Direct Bilirubin

Time frame: Month 9. Number. Unit: participants

Measure	Single Arm n = 11
Value	11

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 9 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Single Arm	0 of 11 (0%)	1 of 11 (9.1%)	0 of 11

Limitations and caveats (from the sponsor): The last patient enrolled in the study was on 11/8/2016. Due to decreased enrollment permission was granted by the Atrium Health IRB to officially close the study to new enrollees on May 31, 2019. The last patient enrolled is now 5 years removed from enrollment date.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: 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.
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.
Individual participant dataSharing planned: No. Upon study completion

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.

Ricardo A. Caicedo, MD principal investigator

Levine Children's Hospital at Carolinas HealthCare System

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 Total Parenteral Nutrition-induced Cholestasis, run by Wake Forest University Health Sciences 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 6 inclusion and 7 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 23 Nov 2022. 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 23 Nov 2022). 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?

Number of Participants With Normalization of Direct Bilirubin (time frame: Month 9). 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 NCT01845116, which also lists 3 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 23 Nov 2022.