Effect of Fish Oil Emulsion on Liver Disease in Patients With Long-term Intravenous Nutrition
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Purpose
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 over 6 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 in those receiving fish-oil also at the end of the study. 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Total Parenteral Nutrition-induced Cholestasis |
Drug: Soybean oil based emulsion Drug: Soybean oil based emulsion+Fish oil based emulsion |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Effect of n-3 Polyunsaturated Fatty Acid Lipid Emulsion on Parenteral Nutrition Associated Liver Disease |
- Change in plasma total bilirubin between baseline and 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Change in total bilirubin between baseline and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Changes in liver function test (ALP, AST, GGT) between baseline and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Changes in liver histology between baseline and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]second liver biopsies only done in patients receiving the experimental drug (fish oil supplementation)
- Changes in liver fatty acid composition between baseline and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Changes in liver oxidative stress between baseline and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Changes in liver gene expression between baseline and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | February 2012 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Intralipid+ Omegaven
10 patients will receive Intralipid (0.25 g/kg/TPN day) + Omegaven (0.4 g/kg/TPN day) for a period of 6 months.
|
Drug: Soybean oil based emulsion+Fish oil based emulsion
Intralipid+Omegaven: 0.25 g/kg/TPN Intralipid day+0.4 g/kg/TPN Omegaven day for 6 months
Other Name: Intralipid, Omegaven
|
|
Active Comparator: Standard treatment (Intralipid)
10 patients will receive Intralipid (0.25 g/kg/TPN day) for a period of 6 months.
|
Drug: Soybean oil based emulsion
1. Soybean oil based emulsion: 0.25 g/kg/TPN day
Other Name: Intralipid
|
Detailed Description:
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. The primary objective is to study the effect of 3 months of Omegaven supplementation on plasma total bilirubin. Secondary objectives are to study the effect of 6 months of Omegaven supplementation on bilirubin, liver enzymes, liver histology, liver fatty acid composition, lipid peroxidation, antioxidants, and gene expression. Fasting glucose and insulin will also be measured. 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 bloodwork 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 6 months. Bloodwork will be repeated after 3 months of the initiation of the intervention and at the end. The group that receives the Omegaven supplementation will also have a repeat liver biopsy done. In the 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 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
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Clinically stable patients on home TPN with PNALD with persistently elevated bilirubin (>1.5 times > normal) for at least 3 months despite standard treatment with ursodeoxycholic acid (15-30 mg/kg or at least 500 mg/d orally), changes in TPN (reduction to 25 kcal/kg/TPN day with Intralipid 0.25 g/kg) , and antibiotics (Metronidazole 500 mg bid and Ciprofloxacin 500 mg bid)
- male or female,equal or over 18 years of age
- on stable TPN regimen equal or over 3 days/week
- on a stable drug regimen for equal or over 3 months prior to randomization, which will not changed for the study duration if these drugs are ursodeoxycholic acid given for PNALD or others affecting glucose and lipid metabolism
Exclusion Criteria:
- Not receiving lipid emulsion as part of TPN
- Allergy to fish, egg , soy, and peanuts
- Liver disease of other etiology (e.g. excessive alcohol intake >20g/d, viral hepatitis, auto-immune or drug-induced, hemochromatosis, alfa 1-antitrypsin deficiency, Wilson's disease)
- Complications of chronic liver disease, such as recurrent variceal bleeding, ascites, encephalopathy or any other reason contraindicating a liver biopsy
- Severe hemorrhagic disorders
- Sepsis - Inflammatory processes
- Taking medications that precipitate steatohepatitis (e.g. corticosteroids, methotrexate, or amiodarone)
- Pregnancy, lactation
- Fluid restriction - Omegaven is more dilute than Intralipid.
Contacts and Locations| Contact: Johane P Allard, MD,FRCPC | 416-340-5159 | johane.allard@uhn.on.ca |
| Contact: Bianca M Arendt, PhD | 416-340-4104 | barendt@uhnresearch.ca |
| Canada, Alberta | |
| Foothills Medical Center | Not yet recruiting |
| Calgary, Alberta, Canada, T2N 4Z6 | |
| Contact: Maitreyi Raman, MD Maitreyi.raman@gmail.com | |
| Principal Investigator: Maitreyi Raman, MD | |
| University of Alberta | Recruiting |
| Edmonton, Alberta, Canada, T5H 3V9 | |
| Contact: Leah Gramlich, MD 780-421-1029 leah.gramlich@ualberta.ca | |
| Principal Investigator: Leah Gramlich, MD | |
| Canada, Manitoba | |
| St Boniface Hospital | Not yet recruiting |
| Winnipeg, Manitoba, Canada, R2H 2A6 | |
| Contact: Donald Duerksen, MD dduerkse@sbgh.mb.ca | |
| Principal Investigator: Donald Duerksen, MD | |
| Canada, Ontario | |
| University Health Network | Recruiting |
| Toronto, Ontario, Canada, M5G 2N2 | |
| Contact: Johane P Allard, MD,FRCPC 416-340-5159 johane.allard@uhn.on.ca | |
| Contact: Bianca M Arendt, PhD 416-340-4104 barendt@uhnresearch.ca | |
| Principal Investigator: Johane P Allard, MD,FRCPC | |
| Principal Investigator: | Johane P Allard, MD,FRCPC | University Health Network, Toronto |
More Information
Publications:
| Responsible Party: | University Health Network, Toronto |
| ClinicalTrials.gov Identifier: | NCT01565278 History of Changes |
| Other Study ID Numbers: | 11-0298-B, 151342 |
| Study First Received: | March 26, 2012 |
| Last Updated: | March 28, 2012 |
| Health Authority: | Canada: Health Canada |
Keywords provided by University Health Network, Toronto:
|
Parenteral nutrition fish oil liver disease Omegaven |
hepatic liver biopsy bilirubin |
Additional relevant MeSH terms:
|
Cholestasis Liver Diseases Bile Duct Diseases Biliary Tract Diseases Digestive System Diseases |
ClinicalTrials.gov processed this record on May 21, 2013