The Effect of Fish Oils on Human Hepatic Colorectal Metastases

This study has been completed.
Sponsor:
Collaborator:
B. Braun Melsungen AG
Information provided by (Responsible Party):
University Hospitals, Leicester
ClinicalTrials.gov Identifier:
NCT00942292
First received: July 16, 2009
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine whether fish oils - a known source of omega-3 given intravenously (via a 'drip') will help cure secondary deposits in the liver from bowel cancer.


Condition Intervention Phase
Colorectal Liver Metastases
Dietary Supplement: Lipidem- fish oil emulsion BBraun UK
Procedure: Digital Contrast MRI scan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomised Controlled Trial of the Effects of Fish Oil Emulsion in Total Parenteral Nutrition Upon Tumour Vascularity in Patients With Hepatic Colorectal Metastases

Resource links provided by NLM:


Further study details as provided by University Hospitals, Leicester:

Primary Outcome Measures:
  • Change in gadolinium chelate enhancement on DCE-MRI between study entry and exit, as determined by calculating the bi-directional transfer co-efficient.(Changes in tumour angiogenesis after treatment with fish oils or control TPN) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in biomarkers of inflammation and angiogenesis in the patient's blood and resected tumour samples [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: May 2007
Study Completion Date: October 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lipidem (fish oil)
Lipidem (TPN containing fish oil)
Dietary Supplement: Lipidem- fish oil emulsion BBraun UK Procedure: Digital Contrast MRI scan
Active Comparator: Lipofundin (TPN)
Control arm (no fish oil)
Dietary Supplement: Lipidem- fish oil emulsion BBraun UK Procedure: Digital Contrast MRI scan

Detailed Description:

Fish oils have many proven benefits for a wide range of clinical arenas such as ischaemic heart disease, rheumatoid arthritis and inflammatory bowel disease.

Recent research has described the beneficial effects of intravenous fish oils for surgical patients, such as reduced hospital stay, reduced re-operation rate and reduced requirements for intravenous antibiotics. These are in part due to the anti-inflammatory effects of fish oils.

There is evidence that fish oils are also effective against cancer, large population studies indicate that diets rich in omega-3 are associated with a lower incidence of cancer, and in vitro and animal studies demonstrate anti-tumour effects of fish oils

  1. Fish oils inhibit the growth of different human cancer cell lines
  2. They act specifically on tumour cells only and do not impair the function of normal cells
  3. EPA and DHA inhibit the growth of human cancer cell lines and enhance apoptosis.
  4. Fish oil induces apoptosis in human colorectal cancer cell lines in-vitro after 48hrs incubation
  5. Fish oil has been shown to inhibit the proliferation activities, inhibit the invasive activities and increase the apoptosis of human pancreatic carcinoma cell lines in-vitro after only 48hrs of exposure
  6. Fish oil has been shown to enhance colorectal adenocarcinoma cell lines sensitivity to radiotherapy
  7. Fish oil has also been shown to reduce the incidence of liver metastases in experimentally induced ductal pancreatic cancer in rats after 30 weeks of oral treatment with an omega-3 supplemented diet.
  8. Lung cancer xenografts in animals fed with fish oil showed significantly increased tumour regression in response to doxorubicin compared to those fed with omega-3.

This study aims to assess the effect of omega-3 FA upon hepatic colorectal metastases in a pilot study. 20 patients will be selected for this pilot study with potentially resectable hepatic colorectal adenocarcinoma metastases. 10 patients will receive total parenteral nutrition (TPN) without fish oils (controls), 10 will receive fish oil containing lipid emulsion in their TPN.

Changes in tumour angiogenesis (increased angiogenesis is associated with a poorer prognosis in hepatic colorectal metastases) will be investigated using digital contrast enhanced MRI scanning, and markers of angiogenesis will be investigated in blood and resected tumour samples from the patients.

It is a randomised controlled double blind trial.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18-80
  2. Able to give informed written consent
  3. Diagnosis of respectable hepatic colorectal metastases on radiological and laparoscopic appearances

Exclusion Criteria:

  1. Patients already taking fish oil supplements
  2. Hypersensitivity to fish-, egg-, or soy protein, or to any of the active substances or constituents in the lipid emulsion
  3. Hyperlipidaemia
  4. Severe blood coagulation disorders
  5. Severe renal insufficiency (Creatinine >200)
  6. Any general contra-indications to infusion therapy - pulmonary oedema, hyperhydration, decompensated cardiac insufficiency
  7. Any unstable medical conditions - uncontrolled diabetes mellitus, acute myocardial infarction, stroke, embolic disease, metabolic acidosis, sepsis, pancreatitis
  8. Patients undergoing conventional neo-adjuvant chemotherapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00942292

Locations
United Kingdom
Leicester General Hospital
Leicester, Leicestershire, United Kingdom, LE5 4PW
Sponsors and Collaborators
University Hospitals, Leicester
B. Braun Melsungen AG
Investigators
Principal Investigator: Ashley R Dennison, MBChB, FRCS, MD Leicester General Hospital
  More Information

Publications:
Schulzki, C., et al., Effect of a new type of lipid emulsion base on soybean oil, MCT, olive oil and fish oil (SMOF) in surgical patients. Clinical Nutrition, 1999. 19(Supp 1): p. S7.
Weiss, G., et al., Immunomodulation by peri-operative administrateion of omega-3 fatty acids. British Journal of Nutrition, 2002. 87(Suppl 1): p. S89-94.
Grimminger, F., W. Seeger, and K. Mayer, Use of omeg-3 fatty acid-containing lipid emulsions in the intensive care unit environment: the clinician's view. Clinical Nutrition, 2002. 21(2): p. 23-9.
Grimble, R., et al., Effects of fish oil supplementation on ability of monocytes to invoke a pro-inflammatory response in endothelial cells. Clinical Nutrition, 2004. 23(4): p. 833-834.
Morlion, B., et al., What is the optimum omega-3 to omega-6 fatty acid (FA) ratio of patenteral lipid emulsions in post-operative trauma? Clinical Nutrition, 1997. 16(Suppl 2): p. 49.
Adolph, M., Lipid emulsions in parenteral nutrition - state of the art and future perspectives. Clinical Nutrition, 2001. 20(Suppl 4): p. 1
Grecu, I., L. Mirea, and I. Grintescu, Parenteral fish oil supplementation in patients with abdominal sepsis. Clinical Nutrition, 2003. 22: p. S23
Heller, A., J. Striebel, and T. Koch, Effects of fish-oil supplementation on the clinical course of critical illness. A multicenter trial. European Journal of Anesthesiology, 2003. 20: p. 157.
Kelbel, I., et al., Effects of omega-3 fatty acids on immune function: a double-blind, randomized trial of fish oil based infusion in post-operative patients. Clinical Nutrition, 2002. 21: p. 13-14.
Wichmann, M., et al., Reduction of length of post-operative stay by fish oil containing lipid emulsion - data from a multicenter trial. Clinical Nutrition, 2004. 23
Llor, X., et al., Involvement of the intrinsic and extrinsic pathways in the apoptosis-inducing effect of the n-3 fatty acid docosahexanoic on colorectal cancer cells. Clinical Nutrition, 2004. 23(4): p. 891.
Shirota, T., et al., Suppression of human pancreatic carcinoma cell growth and invasion by eicosapentaenoic acid. Clinical Nutrition, 2004. 23(4): p. 888-889
Wenger, F., et al., Impact of dietary fact on hepatic metastases and lipidperoxidation in pancreatic cancer. Clinical Nutrition, 2004. 23(4): p. 788-789.
Benais-Pont, G., Y. Dupertuis, and C. Pichard, Influence of polyunsaturated fatty acids on the growth and radio-sensitivity of three human colorectal adenocarcinoma cell lines. Clinical Nutrition, 2004. 23(4): p. 801
Sturlan, S., et al., Long-chain omega-3 polyunsaturated fatty acids enhance arsenic trioxide cytotoxicity in breast cancer cells. Clinical Nutrition, 2004. 23(4): p. 797
Tappy, L., et al., Metabolic effects of parenteral nutrition with or without omega-3 fatty acids. Clinical Nutrition, 2003. 22: p. S50.
Schlotzer, E., et al., Intravenous application of a fish oil emulsion. Akt Ernahr Med, 1992. 17: p. 170-5.
Richelle, M., et al., Does fish oil supplementation effect the intravascular effect of LCT emulsion in man. Clinical Nutrition, 1993: p. 12.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospitals, Leicester
ClinicalTrials.gov Identifier: NCT00942292     History of Changes
Other Study ID Numbers: 10097, REC reference: 06/Q2501/160, EudraCT number: 2006-000044-71
Study First Received: July 16, 2009
Last Updated: June 24, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by University Hospitals, Leicester:
Hepatic
colorectal
metastases
TPN
Fish oil

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on April 21, 2014