Colorectal Liver MetastasesPhase 2NCT00942292
The Effect of Fish Oils on Human Hepatic Colorectal Metastases
A Phase 2 study testing Lipidem- fish oil emulsion BBraun UK and Digital Contrast MRI scan in people with Colorectal Liver Metastases, run by University Hospitals, Leicester at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Liver Metastases
- What is being tested?
- Lipidem- fish oil emulsion BBraun UK and Digital Contrast MRI scan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2007to Oct 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-80
- Able to give informed written consent
- Diagnosis of respectable hepatic colorectal metastases on radiological and laparoscopic appearances
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leicester General Hospital
Leicester, Leicestershire, LE5 4PW
About this study
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
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.
Read the 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
- Fish oils inhibit the growth of different human cancer cell lines
- They act specifically on tumour cells only and do not impair the function of normal cells
- EPA and DHA inhibit the growth of human cancer cell lines and enhance apoptosis.
- Fish oil induces apoptosis in human colorectal cancer cell lines in-vitro after 48hrs incubation
- 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
- Fish oil has been shown to enhance colorectal adenocarcinoma cell lines sensitivity to radiotherapy
- 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.
- 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.
- Conditions
- Colorectal Liver Metastases
- Being tested
- Lipidem- fish oil emulsion BBraun UK, Digital Contrast MRI scan
- Keywords
- Hepatic, colorectal, metastases, TPN, Fish oil
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipidem- fish oil emulsion BBraun UKDietary supplement
Digital Contrast MRI scanProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Lipidem (fish oil) | Active comparator | Lipidem (TPN containing fish oil) Receives: Dietary Supplement: Lipidem- fish oil emulsion BBraun UK; Procedure: Digital Contrast MRI scan |
| Lipofundin (TPN) | Active comparator | Control arm (no fish oil) Receives: Dietary Supplement: Lipidem- fish oil emulsion BBraun UK; Procedure: Digital Contrast MRI scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 72 hours
Secondary outcomes (1)
Changes in biomarkers of inflammation and angiogenesis in the patient's blood and resected tumour samples
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2009 (estimated)
- Study startMay 2007
- Primary completionDec 2009
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (59)Papers the sponsor has linked to this study.
- Other trials for Colorectal Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals, Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- B. Braun Melsungen AG
- Responsible party
- Sponsor
- Investigators
- Ashley R Dennison, MBChB, FRCS, MD, Principal investigator, Leicester General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00942292
- Sponsor's protocol ID
- 10097
- Other IDs
- REC reference: 06/Q2501/160, EudraCT number: 2006-000044-71
- Status last verified
- Jun 2013
- First submitted
- 16 Jul 2009
- Last updated
- 25 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 8843174Roulet 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.
PubMed 9323693Schauder 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.
PubMed 11895146Mayer 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.
PubMed 12897994Mayer 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.
PubMed 12615625Schulzki, 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, 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.
PubMed 11895158Grimminger, 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.
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.
PubMed 10700528Adolph, M., Lipid emulsions in parenteral nutrition - state of the art and future perspectives. Clinical Nutrition, 2001. 20(Suppl 4): p. 1
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.
PubMed 7815672Grimm 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.
PubMed 11685569Grecu, I., L. Mirea, and I. Grintescu, Parenteral fish oil supplementation in patients with abdominal sepsis. Clinical Nutrition, 2003. 22: p. S23
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00942292
- Acronym / sponsor ID
- 10097
- Conditions
- Colorectal Liver Metastases
- Keywords
- Hepatic, colorectal, metastases, TPN, Fish oil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospitals, LeicesterUniversity, hospital or other
- Collaborators
- B. Braun Melsungen AG
- Study start
- May 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 20 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Fish oils inhibit the growth of different human cancer cell lines
- They act specifically on tumour cells only and do not impair the function of normal cells
- EPA and DHA inhibit the growth of human cancer cell lines and enhance apoptosis.
- Fish oil induces apoptosis in human colorectal cancer cell lines in-vitro after 48hrs incubation
- 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
- Fish oil has been shown to enhance colorectal adenocarcinoma cell lines sensitivity to radiotherapy
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lipidem (fish oil) | Active comparator | Dietary Supplement: Lipidem- fish oil emulsion BBraun UK, Procedure: Digital Contrast MRI scanLipidem (TPN containing fish oil) |
| Lipofundin (TPN) | Active comparator | Dietary Supplement: Lipidem- fish oil emulsion BBraun UK, Procedure: Digital Contrast MRI scanControl arm (no fish oil) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Aged 18-80
- Able to give informed written consent
- Diagnosis of respectable hepatic colorectal metastases on radiological and laparoscopic appearances
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lipidem- fish oil emulsion BBraun UK | Dietary supplement | Lipidem (fish oil), Lipofundin (TPN) |
| Digital Contrast MRI scan | Procedure or surgery | Lipidem (fish oil), Lipofundin (TPN) |
Primary outcome
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
1 secondary outcome
Changes in biomarkers of inflammation and angiogenesis in the patient's blood and resected tumour samples
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2013.
- Background: PubMed 8843174Morlion 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.
- Background: PubMed 9323693Roulet 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.
- Background: PubMed 11895146Schauder 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.
- Background: PubMed 12897994Mayer 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.
- Background: PubMed 12615625Mayer 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.
- BackgroundSchulzki, 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: PubMed 11895158Weiss 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.
- BackgroundGrimminger, 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.
- BackgroundGrimble, 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.
- BackgroundMorlion, 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: PubMed 10700528Furst 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.
- BackgroundAdolph, M., Lipid emulsions in parenteral nutrition - state of the art and future perspectives. Clinical Nutrition, 2001. 20(Suppl 4): p. 1
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashley R Dennison, MBChB, FRCS, MD principal investigator
Leicester General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lipidem- fish oil emulsion BBraun UK and Digital Contrast MRI scan in people with Colorectal Liver Metastases, run by University Hospitals, Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00942292, which also lists 59 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2013.