A Phase 3 interventional study of Soybean oil (Standard treatment) and Soybean oil + Fish oil in Total Parenteral Nutrition-induced Cholestasis, sponsored by Johane Allard. Terminated at 4 sites in Canada. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-05-12.
Sponsored by Johane Allard · Phase 3, Interventional, and Treatment
Patients who are not able to eat normally for a longer time require parenteral nutrition, i.e. they receive liquids and nutrients directly into their veins. This can have many long-term side effects, including liver problems. This study will examine whether a specific lipid emulsion containing fish oil can improve liver disease in patients on parenteral nutrition. The investigators will compare changes in bilirubin and liver enzymes after 3 months in 10 patients receiving standard lipid emulsion to 10 patients receiving standard lipids + a fish-oil containing emulsion. The investigators will also assess liver histology, the kind of fat, oxidative stress and gene expression in the liver at the beginning and after 6 months of fish-oil. The investigators also want to compare the baseline values from all 20 patients to 20 healthy controls. This will help to explain how fish oil may improve liver disease in patients on parenteral nutrition.
Chronic exposure to total parenteral nutrition (TPN) can cause parenteral nutrition associated liver disease (PNALD), a progressive condition that may severely affect the liver and lead to end-stage liver disease. Fish oil has been shown to exert beneficial effects as it favorably alters metabolism and inflammation. It has been used parenterally (Omegaven) in young children with short bowel syndrome and PNALD with encouraging results. In adults it has mostly been used in peri-surgical settings as well as in critically ill patients, again proving its effectiveness.
The goal of this proposal is to show that Omegaven use in home-TPN patients with PNALD and elevated bilirubin despite conventional treatment, is beneficial in improving cholestasis and reducing intrahepatic inflammation. Primary objective is to compare the response to treatment between the Omegaven and the Intralipid group. Secondary objectives are to study the effect of Omegaven supplementation on single liver function tests, liver histology, liver fatty acid composition, liver oxidative stress and gene expression. In addition, the investigators want to compare the baseline values of all 20 patients to 20 healthy controls subjects.
After establishing that the patients' liver disease does not improve with conventional medical treatments for 3 months, as evidenced by repeated blood work at that time, they will all have a liver biopsy done as per diagnostic standards. They will then be randomized to either continue receiving Intralipid (0.25 g/kg/TPN day) or a mixture of Intralipid (0.25 g/kg/TPN day) and Omegaven (0.4 g/kg/TPN day) for a period of 3 months. After that, patients in the Omegaven arm will continue their treatment for 3 more months. Those in the Intralipid arm will be switched over to also receive Omegaven for the following 6 months.
Blood work will be repeated every 3 months after the initiation of the intervention. A repeat liver biopsy will be done in both groups after 6 months.
Main outcome is response to treatment (improvement in liver function tests) after 3 months (comparing Intralipid to Omegaven). In addition, change in liver function tests during the 6 months on Omegaven will be assessed. Lipid peroxidation and oxidative stress, fatty acid composition, and gene expression in the liver will be compared before and after 6 months on Omegaven.
In a second part of the study baseline values from all 20 patients will be compared to 20 healthy controls. Controls will be recruited from the healthy living liver donor transplant program at the University Health Network (UHN). Liver samples will be obtained at the time of hepatectomy for transplantation. The same measurements as for the patient livers will be performed in healthy liver tissue.
Significance: The investigators aim to reveal the beneficial effects of fish oil supplementation in the setting of PNALD. Should this pilot study show improvement in the liver disease with Omegaven, a larger, randomized trial should follow. Comparison with healthy controls will provide further insight into the pathogenesis of PNALD, which to date is not completely understood
99 studies on the registry are indexed under Hyperphagia; 26 are open to participants now.
This study's enrollment of 2 is below the median of 50 across 85 interventional studies indexed under Hyperphagia.
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Exclusion Criteria:
Intralipid (0.25 g/kg/TPN day) + Omegaven (0.4 g/kg/TPN day) for a period of 6 months.
Drug: Soybean oil + Fish oil
Standard treatment: Intralipid (0.25 g/kg/TPN day) for a period of 6 months
Drug: Soybean oil (Standard treatment)
1\. Standard treatment: Soybean oil based emulsion: 0.25 g/kg/TPN day
Also known as: Intralipid
Drug pages: Soybean Oil · Fish Oils
Intralipid+Omegaven: 0.25 g/kg/TPN Intralipid day+0.4 g/kg/TPN Omegaven day for 6 months
Also known as: Intralipid, Omegaven
Response to treatment at 3 months
Response is defined as improvement of at least one PNALD parameter by 20% or more; PNALD parameters are: ALP, GGT, ALT, total bilirubin Yes/No
Time frame: 3 months
Change in total and conjugated bilirubin over time
Time frame: 0, 3, 6 months on Omegaven
Changes in liver function test (ALP, AST, GGT) over 6 months
Time frame: 0, 3, 6 months on Omegaven
Changes in liver histology between baseline and 6 months on Omegaven
Time frame: 0, 6 months on Omegaven
Changes in liver fatty acid composition between baseline and 6 months on Omegaven
Fatty acid composition by gas chromatography
Time frame: 0, 6 months on Omegaven
Changes in liver oxidative stress between baseline and 6 months
Lipid peroxides in liver tissue (test-kit)
Time frame: 0, 6 months
Changes in hepatic gene expression between baseline and 6 months on Omegaven
Hepatic gene expression (mRNA) by microarray
Time frame: 0, 6 months on Omegaven
Insulin resistance
HOMA-insulin resistance 0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven after 3 months
Time frame: 0, 3, 6, 9 months
Blood lipid profile
Triglycerides, total cholesterol, LDL, HDL 0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven after 3 months
Time frame: 0, 3, 6, 9 months
Complete blood count (CBC)
0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven after 3 months
Time frame: 0, 3, 6, 9 months
international normalized ratio (INR)
0, 3, 6 months in Omegaven group 0, 3, 6, 9 months in Intralipid-group switching to Omegaven
Time frame: 0, 3, 6, 9 months
The record gives a start of Feb 2012, a primary completion of Aug 2015 and a completion of Aug 2015. It does not say whether these dates are actual or estimated.
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This study is terminated, as verified in May 2016. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Soybean Oil · Fish Oils
Johane Allard