NCT01565278

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Feb 2012

Typical duration for phase_3

Geographic Reach
1 country

4 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2012

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 26, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 28, 2012

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
Last Updated

May 12, 2016

Status Verified

May 1, 2016

Enrollment Period

3.5 years

First QC Date

March 26, 2012

Last Update Submit

May 10, 2016

Conditions

Total Parenteral Nutrition-induced Cholestasis

Keywords

Parenteral nutritionfish oilliver diseaseOmegavenhepaticliver biopsybilirubin

Outcome Measures

Primary Outcomes (1)

  • 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

    3 months

Secondary Outcomes (6)

  • Change in total and conjugated bilirubin over time

    0, 3, 6 months on Omegaven

  • Changes in liver function test (ALP, AST, GGT) over 6 months

    0, 3, 6 months on Omegaven

  • Changes in liver histology between baseline and 6 months on Omegaven

    0, 6 months on Omegaven

  • Changes in liver fatty acid composition between baseline and 6 months on Omegaven

    0, 6 months on Omegaven

  • Changes in liver oxidative stress between baseline and 6 months

    0, 6 months

  • +1 more secondary outcomes

Other Outcomes (4)

  • Insulin resistance

    0, 3, 6, 9 months

  • Blood lipid profile

    0, 3, 6, 9 months

  • Complete blood count (CBC)

    0, 3, 6, 9 months

  • +1 more other outcomes

Study Arms (2)

Soybean oil + Fish oil

EXPERIMENTAL

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

Soybean oil (Standard treatment)

ACTIVE COMPARATOR

Standard treatment: Intralipid (0.25 g/kg/TPN day) for a period of 6 months

Drug: Soybean oil (Standard treatment)

Interventions

Soybean oil (Standard treatment)DRUG

1\. Standard treatment: Soybean oil based emulsion: 0.25 g/kg/TPN day

Also known as: Intralipid
Soybean oil (Standard treatment)
Soybean oil + Fish oilDRUG

Intralipid+Omegaven: 0.25 g/kg/TPN Intralipid day+0.4 g/kg/TPN Omegaven day for 6 months

Also known as: Intralipid, Omegaven
Soybean oil + Fish oil

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Foothills Medical Center

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta

Edmonton, Alberta, T5H 3V9, Canada

Location

St Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (10)

  • Raman M, Gramlich L, Whittaker S, Allard JP. Canadian home total parenteral nutrition registry: preliminary data on the patient population. Can J Gastroenterol. 2007 Oct;21(10):643-8. doi: 10.1155/2007/217897.

    PMID: 17948134BACKGROUND

  • Fernandes G, Kaila B, Jeejeebhoy KN, Gramlich L, Armstrong D, Allard JP. Canadian home parenteral nutrition (HPN) registry: validation and patient outcomes. JPEN J Parenter Enteral Nutr. 2012 Jul;36(4):407-14. doi: 10.1177/0148607111434599. Epub 2012 Feb 10.

    PMID: 22326909BACKGROUND

  • Jurewitsch B, Gardiner G, Naccarato M, Jeejeebhoy KN. Omega-3-enriched lipid emulsion for liver salvage in parenteral nutrition-induced cholestasis in the adult patient. JPEN J Parenter Enteral Nutr. 2011 May;35(3):386-90. doi: 10.1177/0148607110382023.

    PMID: 21527601BACKGROUND

  • Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006 Feb;130(2 Suppl 1):S70-7. doi: 10.1053/j.gastro.2005.10.066.

    PMID: 16473076BACKGROUND

  • Guglielmi FW, Boggio-Bertinet D, Federico A, Forte GB, Guglielmi A, Loguercio C, Mazzuoli S, Merli M, Palmo A, Panella C, Pironi L, Francavilla A. Total parenteral nutrition-related gastroenterological complications. Dig Liver Dis. 2006 Sep;38(9):623-42. doi: 10.1016/j.dld.2006.04.002. Epub 2006 Jun 12.

    PMID: 16766237BACKGROUND

  • Messing B, Joly F. Guidelines for management of home parenteral support in adult chronic intestinal failure patients. Gastroenterology. 2006 Feb;130(2 Suppl 1):S43-51. doi: 10.1053/j.gastro.2005.09.064.

    PMID: 16473071BACKGROUND

  • Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW. Changing the paradigm: omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):209-15. doi: 10.1097/MPG.0b013e318182c8f6.

    PMID: 19179884BACKGROUND

  • Calhoun AW, Sullivan JE. Omegaven for the treatment of parenteral nutrition associated liver disease: a case study. J Ky Med Assoc. 2009 Feb;107(2):55-7.

    PMID: 19263944BACKGROUND

  • Chung PH, Wong KK, Wong RM, Tsoi NS, Chan KL, Tam PK. Clinical experience in managing pediatric patients with ultra-short bowel syndrome using omega-3 fatty acid. Eur J Pediatr Surg. 2010 Mar;20(2):139-42. doi: 10.1055/s-0029-1238283. Epub 2010 Feb 22.

    PMID: 20178080BACKGROUND

  • Fallon EM, Le HD, Puder M. Prevention of parenteral nutrition-associated liver disease: role of omega-3 fish oil. Curr Opin Organ Transplant. 2010 Jun;15(3):334-40. doi: 10.1097/mot.0b013e3283394879.

    PMID: 20503524BACKGROUND

MeSH Terms

Conditions

HyperphagiaLiver Diseases

Interventions

Soybean Oilsoybean oil, phospholipid emulsionFish Oilsfish oil triglycerides

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsDigestive System Diseases

Intervention Hierarchy (Ancestors)

Dietary Fats, UnsaturatedDietary FatsFatsLipidsFats, UnsaturatedPlant OilsOilsPlant PreparationsBiological ProductsComplex MixturesFoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Johane P Allard, MD,FRCPC

    University Health Network, Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Medicine, Gastroenterologist

Study Record Dates

First Submitted

March 26, 2012

First Posted

March 28, 2012

Study Start

February 1, 2012

Primary Completion

August 1, 2015

Study Completion

August 1, 2015

Last Updated

May 12, 2016

Record last verified: 2016-05

Locations

CA(4)