Omegaven for Essential Fatty Acid Deficiency

Recruiting at 9 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Omegaven®, a fish oil-based treatment, for safety in children with Parenteral Nutrition-Associated Cholestasis, a liver condition related to intravenous feeding. The goal is to provide essential calories and fatty acids to children unable to eat normally due to digestive issues. Children diagnosed with this liver problem and who have difficulty eating normally might be suitable candidates for this trial.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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 is the safety track record for Omegaven®?

Research shows that Omegaven® is generally safe and well-tolerated. Studies have found that using fish oil through an IV, like Omegaven®, is safe for long-term use and doesn't cause major side effects for most people. Specifically, research on adults with long-term health issues has shown it to be effective without major safety concerns.

While less information exists about its use in children, available studies support the overall safety of Omegaven®. No reports of serious unexpected medical problems have been linked to its use in the available research. This suggests that the treatment is likely safe for the patient group in this trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment?

Unlike the standard treatments for essential fatty acid deficiency, which often rely on soybean oil-based emulsions, Omegaven® is derived from fish oil triglycerides. This fish oil emulsion provides a different balance of omega-3 to omega-6 fatty acids, which may offer anti-inflammatory benefits and improved liver function, particularly in patients requiring long-term intravenous nutrition. Researchers are excited about Omegaven because it has the potential to reduce liver complications associated with traditional lipid emulsions, offering a safer alternative for patients with this deficiency.

What evidence suggests that Omegaven® might be an effective treatment for Essential Fatty Acid Deficiency?

Research has shown that Omegaven, a treatment made from fish oil, can effectively prevent and treat Essential Fatty Acid Deficiency (EFAD). Studies have found that increasing essential fatty acids, like those in Omegaven, helps maintain healthy levels of these fats in the blood. In this trial, participants will receive Omegaven alone, which has been observed to prevent EFAD, making it a promising option for those at risk. Administered directly into the veins, it ensures the body receives the necessary nutrients. This treatment is especially important for patients who need nutrition delivered straight to the bloodstream, such as those with certain liver conditions. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/210589s001lbl.pdf

Omegaven (fish oil triglycerides) - accessdata.fda.gov Increasing essential fatty acid intake (enterally or parenterally) is effective in treating and preventing EFAD.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3365554/

Parenteral Fish Oil as Monotherapy Prevents Essential Fatty ... The primary study outcome was the onset of EFAD, defined as a triene:tetraene ratio greater than 0.2. Fatty acid profiles were measured from blood samples ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/210589s003lbl.pdf

Omegaven - accessdata.fda.gov It has not been demonstrated that the clinical outcomes observed in recommended, including monitoring for essential fatty acid deficiency. patients treated ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/16/NCT01845116/Prot_000.pdf

Use of a Fish Oil-Based Intravenous Lipid Emulsion ( ... Omegaven® as monotherapy does not result in the development of essential fatty acid deficiency and it can actually be used to as monotherapy to ...

5. freseniuskabinutrition.com freseniuskabinutrition.com/wp-content/uploads/2020/04/FSK-OMG-101-Resource-Guide-V17.pdf

Omegaven - Fresenius Kabi Increasing essential fatty acid intake (enterally or parenterally) is effective in treating and preventing EFAD. 5.9. Interference with Laboratory Tests. The ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0261561424004047

Safe and well-tolerated long-term parenteral nutrition ... The study's objective was to assess safety and tolerability of an n-3 PUFA-enriched LE in adult patients suffering from chronic intestinal failure (CIF) ...

7. freseniuskabinutrition.com freseniuskabinutrition.com/wp-content/uploads/2020/04/Omegaven-PI.pdf

OMEGAVEN (fish oil triglycerides) injectable emulsion Increasing essential fatty acid intake (enterally or parenterally) is effective in treating and preventing. EFAD. 5.9. Interference with Laboratory Tests. The ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02512718

Safety and Tolerability of Intravenous Fish Oil Lipid ... Our aims are to determine the safety profile (as measured by the number of grade 2 or higher adverse events) and tolerability of intravenous ...