Omegaven for Essential Fatty Acid Deficiency

Recruiting at 4 trial locations

Overseen By Niess Ulf, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Fresenius Kabi

Disqualifiers: Chronic liver disease, Cirrhosis, Transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 56 weeks

40 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Omegaven for treating essential fatty acid deficiency?

Research shows that Omegaven, a fish oil-based treatment, has been promising in reversing liver disease and cholestasis (a liver condition) in infants who rely on parenteral nutrition (nutrition given through the veins). However, while it improves certain liver conditions, it may not always improve liver tissue health. ^{1 2 3 4 5}

Is Omegaven safe for use in humans?

Omegaven, a fish oil-based fat emulsion, has been used safely in infants and children with liver disease related to parenteral nutrition, showing benefits like reduced liver damage and improved liver function. It is considered less harmful to the liver compared to traditional soybean oil emulsions, but monitoring for potential side effects is recommended. ^{1 5 6 7 8}

How does the drug Omegaven differ from other treatments for essential fatty acid deficiency?

Omegaven is unique because it is a fish oil-based lipid emulsion rich in omega-3 fatty acids, unlike standard treatments that typically use omega-6 fatty acids. This composition may offer benefits in managing liver-related complications, as seen in conditions like pediatric short bowel syndrome and intestinal failure-associated liver disease. ^{2 7 9 10 11}

What is the purpose of this trial?

This study will demonstrate safety in pediatric patients with Parenteral Nutrition-Associated Cholestasis treated with Omegaven®, which is indicated as a source of calories and fatty acids in this patient population

Eligibility Criteria

This trial is for pediatric patients under 18 with Parenteral Nutrition-Associated Cholestasis (PNAC), which means they have high bilirubin levels and liver issues without other known causes. They must need Omegaven treatment for at least eight weeks and cannot tolerate oral or enteral feeding due to gastrointestinal disorders.

Inclusion Criteria

My parent or guardian has signed the consent form for me.

My child has PNAC and needs Omegaven treatment for at least 8 weeks.

I cannot eat or digest food normally and need nutrition through IV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Omegaven treatment for Parenteral Nutrition-Associated Cholestasis

56 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Omegaven®

Trial Overview The study tests the safety of using Omegaven®, a fish oil-based emulsion, as a calorie and fatty acid source in children with PNAC who require long-term parenteral nutrition.

Participant Groups

Group I: Single arm OMEGAVEN® (fish oil triglycerides; injectable emulsion) Experimental Treatment 1 Intervention

The dose of investigational drug (study treatment), as well as all other components of the overall nutritional regimen is solely at the discretion of the Investigator. It is assumed the Investigator will use sound medical judgement, follow institutional standards of care regarding the nutrition provided to each patient, and review applicable prescribing information indicating the maximum and recommended dose of Omegaven of 1 g/kg/day infused intravenously over 8 to 24 hours as long as the infusion rate does not exceed 1.5 mL/kg/hour.

Omegaven® is already approved in United States, European Union for the following indications:

Approved in United States as Omegaven for:

• Parenteral Nutrition-Associated Cholestasis (PNAC) in pediatric patients

Approved in European Union as Omegaven for:

• Total parenteral nutrition, including short bowel syndrome

Who Is Running the Clinical Trial?

Fresenius Kabi

Lead Sponsor

Trials

83

Recruited

1,138,000+

Pierluigi Antonelli

Fresenius Kabi

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Degree in Economics from L.U.I.S.S.

Dr. John Young

Fresenius Kabi

Chief Medical Officer since 2023

MD from Harvard Medical School

Findings from Research

Parenteral nutrition using soybean-derived fat emulsions can worsen liver disease and cholestasis in infants, especially those with short bowel syndrome.

Omegaven, a fish-oil emulsion, has shown promise in recent studies for reversing liver disease and cholestasis in PN-dependent infants, suggesting it could be a safer alternative for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Omegaven in treating parenteral nutrition-associated liver disease. Park, KT., Nespor, C., Kerner, J.[2011]

In a study of 7 pediatric patients who received parenteral omega-3 fatty acid (O3FA) lipid emulsion, there was a significant reduction in bilirubin levels, indicating improved liver function before intestinal transplantation.

Despite the improvement in bilirubin levels and lower inflammatory scores, all patients still exhibited advanced hepatic fibrosis, suggesting that O3FA may not effectively prevent liver damage associated with long-term parenteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic explant pathology of pediatric intestinal transplant recipients previously treated with omega-3 fatty acid lipid emulsion. Matsumoto, CS., Kaufman, SS., Island, ER., et al.[2020]

The study found that while Omegaven™, a fish oil parenteral lipid product, improved biochemical markers of cholestasis in six infants, it did not consistently lead to improvements in liver histology, with five infants showing persistent or worsening hepatic fibrosis.

These results suggest that there may be a limited timeframe for the effectiveness of Omegaven™ and raise questions about its superiority compared to newer blended lipid formulations that include various oils.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review on hepatic explant pathology of pediatric intestinal transplant recipients: Is it time for an oil change? Imseis, E., Rhoads, JM.[2018]

Intravenous fish oil lipid emulsions (LE) have shown potential benefits in critically ill patients, including reduced incidence of infections, fewer days on mechanical ventilation, and shorter hospital stays, based on recent systematic reviews and meta-analyses.

Despite these promising findings, the evidence is still limited and more robust studies, including dosing studies, are needed before making definitive recommendations for the use of fish oil LE in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fish oil containing lipid emulsions in critically ill patients: Critical analysis and future perspectives]. Manzanares, W., Langlois, PL.[2018]

In a case study involving 2 patients with irreversible intestinal failure and liver disease, treatment with Omegaven (a parenteral omega-3 fatty acid lipid emulsion) led to biochemical and histological improvements in cholestasis.

Despite these improvements, both patients still exhibited significant portal fibrosis on liver biopsy, indicating that while Omegaven may help with certain liver issues, it does not fully reverse all aspects of liver damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of resolution of portal fibrosis during omega-3 fatty acid lipid emulsion therapy in two patients with irreversible intestinal failure. Soden, JS., Lovell, MA., Brown, K., et al.[2011]

The FDA approved a 100% fish oil intravenous lipid emulsion (Omegaven) in July 2018 for infants and children with parenteral nutrition-associated cholestasis, providing a safer alternative to conventional soybean oil emulsions.

This fish oil emulsion is rich in omega-3 fatty acids and has been shown to be less harmful to the liver compared to traditional lipid sources, making it a beneficial option for patients requiring parenteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Fish Oil Intravenous Lipid Emulsions as Monotherapy in the Pediatric Intestinal Failure Patient: Beyond the Package Insert. Gura, KM., Calkins, KL., Puder, M.[2020]

A newborn with intestinal hypoganglionosis and associated liver disease showed significant improvement after treatment with Omegaven™, a fat emulsion of omega-3 fatty acids, leading to a complete resolution of cholestasis within two weeks.

Omegaven™ effectively reduced liver enzyme levels, indicating its potential as a novel therapy for managing cholestatic liver injury in patients with intestinal failure, although guidelines for treating hypoganglionosis are currently lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal Hypoganglionosis Leading to Intestinal Failure and the Compassionate Use of Omegaven™. Khalaf, R., Karjoo, S., Danielson, P., et al.[2020]

Omegaven™, an omega-3 fatty acid lipid emulsion, significantly reduces inflammatory cytokine signaling in liver cells, which may help protect against parenteral nutrition associated liver disease (PNALD).

Specifically, Omegaven™ decreased TGF-β mediated Smad2/3 signaling by 30% and IL-1 and TNF-α mediated ERK1/2 signaling by up to 78%, suggesting it may improve liver health in children receiving parenteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The molecular impact of omega 3 fatty acids on hepatic pro-inflammatory cytokine signaling. Ventro, GJ., Yang, Y., Chen, M., et al.[2020]

In a study of 12 children with short bowel syndrome and advanced liver disease, treatment with Omegaven led to complete resolution of hyperbilirubinemia in 9 patients within a median of 24 weeks, indicating significant improvement in liver function.

Omegaven was found to be safe, with no complications reported, and it has the potential to change the treatment approach for pediatric short bowel syndrome, allowing more children to avoid liver transplantation and achieve better nutritional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing the paradigm: omegaven for the treatment of liver failure in pediatric short bowel syndrome. Diamond, IR., Sterescu, A., Pencharz, PB., et al.[2009]

Dietary omega-3 fatty acid capsules, particularly those containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to effectively lower plasma triglyceride levels, which may contribute to reduced cardiovascular disease risk.

Analysis of eight commercially available fish oil capsules revealed that the actual content of EPA and DHA closely matched labeled amounts, with mean EPA at 17.3% and DHA at 11.5%, indicating that these supplements can provide significant omega-3 fatty acids as intended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatty acid content of marine oil capsules. Chee, KM., Gong, JX., Rees, DM., et al.[2019]

Omega-3 fatty acids, particularly from fish or fish oil supplements, are effective in significantly reducing blood triglyceride levels, which is beneficial for individuals with hypertriglyceridemia, a condition common in the Arab region.

A prescription form of omega-3 fatty acids has been approved by the USFDA for treating very high triglyceride levels (≥ 500 mg/dl) in adults, and they can enhance the lipid profile even when used alongside statins, suggesting a synergistic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish oil and the management of hypertriglyceridemia. Mattar, M., Obeid, O.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

The use of Omegaven in treating parenteral nutrition-associated liver disease. [2011]

2. United States pubmed.ncbi.nlm.nih.gov

Hepatic explant pathology of pediatric intestinal transplant recipients previously treated with omega-3 fatty acid lipid emulsion. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Review on hepatic explant pathology of pediatric intestinal transplant recipients: Is it time for an oil change? [2018]

4. Spain pubmed.ncbi.nlm.nih.gov

[Fish oil containing lipid emulsions in critically ill patients: Critical analysis and future perspectives]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Failure of resolution of portal fibrosis during omega-3 fatty acid lipid emulsion therapy in two patients with irreversible intestinal failure. [2011]

6. United States pubmed.ncbi.nlm.nih.gov

Use of Fish Oil Intravenous Lipid Emulsions as Monotherapy in the Pediatric Intestinal Failure Patient: Beyond the Package Insert. [2020]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Intestinal Hypoganglionosis Leading to Intestinal Failure and the Compassionate Use of Omegaven™. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

The molecular impact of omega 3 fatty acids on hepatic pro-inflammatory cytokine signaling. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Changing the paradigm: omegaven for the treatment of liver failure in pediatric short bowel syndrome. [2009]

10. United States pubmed.ncbi.nlm.nih.gov

Fatty acid content of marine oil capsules. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Fish oil and the management of hypertriglyceridemia. [2017]