The Effect of Fish Oils on Human Hepatic Colorectal Metastases

NCT00942292 | Completed Phase 2 DMC

• 3 other identifiers: 10097REC reference: 06/Q2501/160EudraCT number: 2006-000044-71
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Liver Metastases

Keywords

Hepatic; colorectal; metastases; TPN; Fish oil

Outcome Measures

Primary Outcomes (1)

• 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)

  72 hours

Secondary Outcomes (1)

• Changes in biomarkers of inflammation and angiogenesis in the patient's blood and resected tumour samples

  14 days

Study Arms (2)

Lipidem (fish oil)

ACTIVE COMPARATOR

Lipidem (TPN containing fish oil)

Dietary Supplement: Lipidem- fish oil emulsion BBraun UK; Procedure: Digital Contrast MRI scan

Lipofundin (TPN)

ACTIVE COMPARATOR

Control arm (no fish oil)

Dietary Supplement: Lipidem- fish oil emulsion BBraun UK; Procedure: Digital Contrast MRI scan

Interventions

Lipidem- fish oil emulsion BBraun UK DIETARY_SUPPLEMENT

Lipidem (fish oil); Lipofundin (TPN)

Digital Contrast MRI scan PROCEDURE

Lipidem (fish oil); Lipofundin (TPN)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients already taking fish oil supplements
• Hypersensitivity to fish-, egg-, or soy protein, or to any of the active substances or constituents in the lipid emulsion
• Hyperlipidaemia
• Severe blood coagulation disorders
• Severe renal insufficiency (Creatinine \>200)
• Any general contra-indications to infusion therapy - pulmonary oedema, hyperhydration, decompensated cardiac insufficiency
• Any unstable medical conditions - uncontrolled diabetes mellitus, acute myocardial infarction, stroke, embolic disease, metabolic acidosis, sepsis, pancreatitis
• Patients undergoing conventional neo-adjuvant chemotherapy.

Sponsors & Collaborators

• University Hospitals, Leicester: lead
• B. Braun Melsungen AG: collaborator

Study Sites (1)

Leicester General Hospital

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

Related Publications (59)

• Morlion BJ, Torwesten E, Lessire H, Sturm G, Peskar BM, Furst P, Puchstein C. The effect of parenteral fish oil on leukocyte membrane fatty acid composition and leukotriene-synthesizing capacity in patients with postoperative trauma. Metabolism. 1996 Oct;45(10):1208-13. doi: 10.1016/s0026-0495(96)90237-1.

  PMID: 8843174 BACKGROUND

• Roulet M, Frascarolo P, Pilet M, Chapuis G. Effects of intravenously infused fish oil on platelet fatty acid phospholipid composition and on platelet function in postoperative trauma. JPEN J Parenter Enteral Nutr. 1997 Sep-Oct;21(5):296-301. doi: 10.1177/0148607197021005296.

  PMID: 9323693 BACKGROUND

• Schauder P, Rohn U, Schafer G, Korff G, Schenk HD. Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period. Br J Nutr. 2002 Jan;87 Suppl 1:S103-10. doi: 10.1079/bjn2001463.

  PMID: 11895146 BACKGROUND

• Mayer K, Fegbeutel C, Hattar K, Sibelius U, Kramer HJ, Heuer KU, Temmesfeld-Wollbruck B, Gokorsch S, Grimminger F, Seeger W. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation. Intensive Care Med. 2003 Sep;29(9):1472-81. doi: 10.1007/s00134-003-1900-2. Epub 2003 Jul 25.

  PMID: 12897994 BACKGROUND

• Mayer K, Gokorsch S, Fegbeutel C, Hattar K, Rosseau S, Walmrath D, Seeger W, Grimminger F. Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis. Am J Respir Crit Care Med. 2003 May 15;167(10):1321-8. doi: 10.1164/rccm.200207-674OC. Epub 2003 Feb 25.

  PMID: 12615625 BACKGROUND

• 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.

  BACKGROUND

• Weiss G, Meyer F, Matthies B, Pross M, Koenig W, Lippert H. Immunomodulation by perioperative administration of n-3 fatty acids. Br J Nutr. 2002 Jan;87 Suppl 1:S89-94. doi: 10.1079/bjn2001461.

  PMID: 11895158 BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• Furst P, Kuhn KS. Fish oil emulsions: what benefits can they bring? Clin Nutr. 2000 Feb;19(1):7-14. doi: 10.1054/clnu.1999.0072. No abstract available.

  PMID: 10700528 BACKGROUND

• Adolph, M., Lipid emulsions in parenteral nutrition - state of the art and future perspectives. Clinical Nutrition, 2001. 20(Suppl 4): p. 1

  BACKGROUND

• Grimm H, Tibell A, Norrlind B, Blecher C, Wilker S, Schwemmle K. Immunoregulation by parenteral lipids: impact of the n-3 to n-6 fatty acid ratio. JPEN J Parenter Enteral Nutr. 1994 Sep-Oct;18(5):417-21. doi: 10.1177/0148607194018005417.

  PMID: 7815672 BACKGROUND

• Grimm H, Kraus A. Immunonutrition--supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients. Langenbecks Arch Surg. 2001 Aug;386(5):369-76. doi: 10.1007/s004230100241.

  PMID: 11685569 BACKGROUND

• Grecu, I., L. Mirea, and I. Grintescu, Parenteral fish oil supplementation in patients with abdominal sepsis. Clinical Nutrition, 2003. 22: p. S23

  BACKGROUND

• 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.

  BACKGROUND

• Tsekos E, Reuter C, Stehle P, Boeden G. Perioperative administration of parenteral fish oil supplements in a routine clinical setting improves patient outcome after major abdominal surgery. Clin Nutr. 2004 Jun;23(3):325-30. doi: 10.1016/j.clnu.2003.07.008.

  PMID: 15158295 BACKGROUND

• 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.

  BACKGROUND

• 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

  BACKGROUND

• Heller AR, Rossel T, Gottschlich B, Tiebel O, Menschikowski M, Litz RJ, Zimmermann T, Koch T. Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients. Int J Cancer. 2004 Sep 10;111(4):611-6. doi: 10.1002/ijc.20291.

  PMID: 15239141 BACKGROUND

• 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.

  BACKGROUND

• Shirota, T., et al., Suppression of human pancreatic carcinoma cell growth and invasion by eicosapentaenoic acid. Clinical Nutrition, 2004. 23(4): p. 888-889

  BACKGROUND

• Jiang YH, Lupton JR, Chang WC, Jolly CA, Aukema HM, Chapkin RS. Dietary fat and fiber differentially alter intracellular second messengers during tumor development in rat colon. Carcinogenesis. 1996 Jun;17(6):1227-33. doi: 10.1093/carcin/17.6.1227.

  PMID: 8681436 BACKGROUND

• Singh J, Hamid R, Reddy BS. Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer Res. 1997 Aug 15;57(16):3465-70.

  PMID: 9270014 BACKGROUND

• Chen ZY, Istfan NW. Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells. Prostaglandins Leukot Essent Fatty Acids. 2000 Nov;63(5):301-8. doi: 10.1054/plef.2000.0218.

  PMID: 11090257 BACKGROUND

• Narayanan BA, Narayanan NK, Reddy BS. Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Int J Oncol. 2001 Dec;19(6):1255-62. doi: 10.3892/ijo.19.6.1255.

  PMID: 11713597 BACKGROUND

• Chiu LC, Wan JM. Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is associated with downregulation of bcl-2 expression. Cancer Lett. 1999 Oct 18;145(1-2):17-27. doi: 10.1016/s0304-3835(99)00224-4.

  PMID: 10530765 BACKGROUND

• Collett ED, Davidson LA, Fan YY, Lupton JR, Chapkin RS. n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes. Am J Physiol Cell Physiol. 2001 May;280(5):C1066-75. doi: 10.1152/ajpcell.2001.280.5.C1066.

  PMID: 11287318 BACKGROUND

• Dommels YE, Alink GM, Linssen JP, van Ommen B. Effects of n-6 and n-3 polyunsaturated fatty acids on gap junctional intercellular communication during spontaneous differentiation of the human colon adenocarcinoma cell line Caco-2. Nutr Cancer. 2002;42(1):125-30. doi: 10.1207/S15327914NC421_17.

  PMID: 12235644 BACKGROUND

• Wenger, F., et al., Impact of dietary fact on hepatic metastases and lipidperoxidation in pancreatic cancer. Clinical Nutrition, 2004. 23(4): p. 788-789.

  BACKGROUND

• Saeki T, Tanada M, Takashima S, Saeki H, Takiyama W, Nishimoto N, Moriwaki S. Correlation between expression of platelet-derived endothelial cell growth factor (thymidine phosphorylase) and microvessel density in early-stage human colon carcinomas. Jpn J Clin Oncol. 1997 Aug;27(4):227-30. doi: 10.1093/jjco/27.4.227.

  PMID: 9379508 BACKGROUND

• O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997 Jan 24;88(2):277-85. doi: 10.1016/s0092-8674(00)81848-6.

  PMID: 9008168 BACKGROUND

• Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther. 1999 Sep;83(3):217-44. doi: 10.1016/s0163-7258(99)00026-1.

  PMID: 10576293 BACKGROUND

• 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

  BACKGROUND

• 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

  BACKGROUND

• Heller AR, Fischer S, Rossel T, Geiger S, Siegert G, Ragaller M, Zimmermann T, Koch T. Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery. Br J Nutr. 2002 Jan;87 Suppl 1:S95-101. doi: 10.1079/bjn2001462.

  PMID: 11895160 BACKGROUND

• Katz DP, Manner T, Furst P, Askanazi J. The use of an intravenous fish oil emulsion enriched with omega-3 fatty acids in patients with cystic fibrosis. Nutrition. 1996 May;12(5):334-9. doi: 10.1016/s0899-9007(96)80056-6.

  PMID: 8875517 BACKGROUND

• Tappy, L., et al., Metabolic effects of parenteral nutrition with or without omega-3 fatty acids. Clinical Nutrition, 2003. 22: p. S50.

  BACKGROUND

• Mertes N, Grimm H, Furst P, Stehle P. Safety and efficacy of a new parenteral lipid emulsion (SMOFlipid) in surgical patients: a randomized, double-blind, multicenter study. Ann Nutr Metab. 2006;50(3):253-9. doi: 10.1159/000091683. Epub 2006 Feb 23.

  PMID: 16508253 BACKGROUND

• Genton, L., et al., Tolerance to a lipid emulsion containing a mixture of soybean, olive, coconut and fish oils compared with a standard fat emulsion containing only soybean oil. Clinical Nutrition, 2004. Abstract ESPEN 2004.

  BACKGROUND

• Antebi H, Mansoor O, Ferrier C, Tetegan M, Morvan C, Rangaraj J, Alcindor LG. Liver function and plasma antioxidant status in intensive care unit patients requiring total parenteral nutrition: comparison of 2 fat emulsions. JPEN J Parenter Enteral Nutr. 2004 May-Jun;28(3):142-8. doi: 10.1177/0148607104028003142.

  PMID: 15141405 BACKGROUND

• Mayer K, Meyer S, Reinholz-Muhly M, Maus U, Merfels M, Lohmeyer J, Grimminger F, Seeger W. Short-time infusion of fish oil-based lipid emulsions, approved for parenteral nutrition, reduces monocyte proinflammatory cytokine generation and adhesive interaction with endothelium in humans. J Immunol. 2003 Nov 1;171(9):4837-43. doi: 10.4049/jimmunol.171.9.4837.

  PMID: 14568963 BACKGROUND

• Schlotzer, E., et al., Intravenous application of a fish oil emulsion. Akt Ernahr Med, 1992. 17: p. 170-5.

  BACKGROUND

• Richelle, M., et al., Does fish oil supplementation effect the intravascular effect of LCT emulsion in man. Clinical Nutrition, 1993: p. 12.

  BACKGROUND

• Moertel CG, Hanley JA. The effect of measuring error on the results of therapeutic trials in advanced cancer. Cancer. 1976 Jul;38(1):388-94. doi: 10.1002/1097-0142(197607)38:13.0.co;2-a.

  PMID: 947531 BACKGROUND

• James K, Eisenhauer E, Christian M, Terenziani M, Vena D, Muldal A, Therasse P. Measuring response in solid tumors: unidimensional versus bidimensional measurement. J Natl Cancer Inst. 1999 Mar 17;91(6):523-8. doi: 10.1093/jnci/91.6.523.

  PMID: 10088622 BACKGROUND

• Yuh WT. An exciting and challenging role for the advanced contrast MR imaging. J Magn Reson Imaging. 1999 Sep;10(3):221-2. doi: 10.1002/(sici)1522-2586(199909)10:33.0.co;2-x. No abstract available.

  PMID: 10508280 BACKGROUND

• Taylor JS, Tofts PS, Port R, Evelhoch JL, Knopp M, Reddick WE, Runge VM, Mayr N. MR imaging of tumor microcirculation: promise for the new millennium. J Magn Reson Imaging. 1999 Dec;10(6):903-7. doi: 10.1002/(sici)1522-2586(199912)10:63.0.co;2-a.

  PMID: 10581502 BACKGROUND

• Buadu LD, Murakami J, Murayama S, Hashiguchi N, Sakai S, Masuda K, Toyoshima S, Kuroki S, Ohno S. Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis. Radiology. 1996 Sep;200(3):639-49. doi: 10.1148/radiology.200.3.8756909.

  PMID: 8756909 BACKGROUND

• Hawighorst H, Knapstein PG, Weikel W, Knopp MV, Zuna I, Knof A, Brix G, Schaeffer U, Wilkens C, Schoenberg SO, Essig M, Vaupel P, van Kaick G. Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement. Cancer Res. 1997 Nov 1;57(21):4777-86.

  PMID: 9354439 BACKGROUND

• Hawighorst H, Weikel W, Knapstein PG, Knopp MV, Zuna I, Schonberg SO, Vaupel P, van Kaick G. Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome. Clin Cancer Res. 1998 Oct;4(10):2305-12.

  PMID: 9796959 BACKGROUND

• Mayr NA, Hawighorst H, Yuh WT, Essig M, Magnotta VA, Knopp MV. MR microcirculation assessment in cervical cancer: correlations with histomorphological tumor markers and clinical outcome. J Magn Reson Imaging. 1999 Sep;10(3):267-76. doi: 10.1002/(sici)1522-2586(199909)10:33.0.co;2-y.

  PMID: 10508286 BACKGROUND

• Erlemann R, Sciuk J, Bosse A, Ritter J, Kusnierz-Glaz CR, Peters PE, Wuisman P. Response of osteosarcoma and Ewing sarcoma to preoperative chemotherapy: assessment with dynamic and static MR imaging and skeletal scintigraphy. Radiology. 1990 Jun;175(3):791-6. doi: 10.1148/radiology.175.3.2188300.

  PMID: 2188300 BACKGROUND

• Fletcher BD, Hanna SL, Fairclough DL, Gronemeyer SA. Pediatric musculoskeletal tumors: use of dynamic, contrast-enhanced MR imaging to monitor response to chemotherapy. Radiology. 1992 Jul;184(1):243-8. doi: 10.1148/radiology.184.1.1319075.

  PMID: 1319075 BACKGROUND

• Reddick WE, Taylor JS, Fletcher BD. Dynamic MR imaging (DEMRI) of microcirculation in bone sarcoma. J Magn Reson Imaging. 1999 Sep;10(3):277-85. doi: 10.1002/(sici)1522-2586(199909)10:33.0.co;2-s.

  PMID: 10508287 BACKGROUND

• Barentsz JO, Berger-Hartog O, Witjes JA, Hulsbergen-van der Kaa C, Oosterhof GO, VanderLaak JA, Kondacki H, Ruijs SH. Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic contrast-enhanced MR imaging. Radiology. 1998 Jun;207(3):791-7. doi: 10.1148/radiology.207.3.9609906.

  PMID: 9609906 BACKGROUND

• Morgan B, Thomas AL, Drevs J, Hennig J, Buchert M, Jivan A, Horsfield MA, Mross K, Ball HA, Lee L, Mietlowski W, Fuxuis S, Unger C, O'Byrne K, Henry A, Cherryman GR, Laurent D, Dugan M, Marme D, Steward WP. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J Clin Oncol. 2003 Nov 1;21(21):3955-64. doi: 10.1200/JCO.2003.08.092. Epub 2003 Sep 29.

  PMID: 14517187 BACKGROUND

• Tsuji M, Murota SI, Morita I. Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor. Prostaglandins Leukot Essent Fatty Acids. 2003 May;68(5):337-42. doi: 10.1016/s0952-3278(03)00025-5.

  PMID: 12711251 BACKGROUND

• Al-Taan O, Stephenson JA, Spencer L, Pollard C, West AL, Calder PC, Metcalfe M, Dennison AR. Changes in plasma and erythrocyte omega-6 and omega-3 fatty acids in response to intravenous supply of omega-3 fatty acids in patients with hepatic colorectal metastases. Lipids Health Dis. 2013 May 7;12:64. doi: 10.1186/1476-511X-12-64.

  PMID: 23648075 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ashley R Dennison, MBChB, FRCS, MD

  Leicester General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2009
• First Posted: July 20, 2009
• Study Start: May 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: October 1, 2010
• Last Updated: June 25, 2013

Record last verified: 2013-06

Locations

GB (1)