Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00510692
Status:
COMPLETED
Last Update Posted:
2014-08-22
First Post:
2007-07-30
Brief Title:
Chemoprevention Trial in Familial Adenomatous Polyposis FAP Coli Using EPA
Sponsor:
SLA Pharma AG
Organization:
SLA Pharma AG
Study Overview
Official Title:
A Two-Arm Chemoprevention Trial in Familial Adenomatous Polyposis FAP Coli Patients Using the Purified Free Fatty Acid Eicosapentaenoic Acid
Status:
COMPLETED
Status Verified Date:
2014-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This purpose of this study is to investigate whether the number and size of rectal polyps can be reduced in patients with Familial Adenomatous Polyposis FAP by using a highly-purified form of a naturally occurring substance the omega-3 fatty acid eicosapentaenoic acid EPA
Detailed Description:
It has been found that people who consume a large amount of oily fish tend to have a lower risk of developing colon cancer This is thought to be due to the omega-3 fatty acids present in oily fish one of which is EPA The effect of taking a 99 pure form of EPA 2g per day compared with placebo capsules on the number and size of polyps in the rectum over a six month period will be investigated
FAP is an inherited susceptibility to diffuse colorectal adenomas and colorectal carcinoma occurring in close to 100 of unresected colons It is caused by a germline mutation in the Adenomatous Polyposis Coli APC gene located in the long arm of chromosome 5 To prevent cancer development it is recommended that patients with FAP undergo colectomy with ileo-anal or ileo-rectal anastomosis or colectomy and end-ileostomy at a socially convenient time before polyp progression to malignancy and before the age of 25 Patients with the attenuated FAP phenotype often associated with mutations at the 5 terminus exon 4 and proximally have fewer polyps and may often delay colectomy Patients with an ileo-rectal anastomosis are still susceptible to polyp formation in the remaining rectal stump and require 6 monthly check-ups with a flexible sigmoidoscope with removal of any polyps that develop Therefore an effective chemopreventative agent with a favourable side-effect profile would be of benefit to FAP patients with ileo-rectal anastomosis IRA and recurrent rectal polyps in addition to young adults who prefer to delay colectomy If such an agent were to be effective in FAP patients in the prevention of colonic polyps it may also be of benefit to the larger population of patients with sporadic colorectal adenomatous polyps who are also at risk of colorectal cancer
Colorectal polyps are thought at least in part to arise from an imbalance in the levels of cell proliferation and apoptosis natural cell death in the colonic mucosa It has been suggested that omega-3 polyunsaturated fatty acids PUFAs in fish oil can manipulate the high levels of colonic-mucosal cell proliferation rates associated with colonic adenomas
The rationale for this trial is based on the increasing evidence linking inflammatory processes and the development of a number of cancers including bowel cancer This has focused attention on the role of inflammatory mediators in the development of cancer In particular the family of eicosanoids including 2-series prostaglandins 4-series leukotrienes and thromboxanes produced through conversion of the omega-6 PUFA arachidonic acid via cyclo-oxygenase-2 COX-2 is believed to contribute to the physiological processes of inflammation and the development of tumours Prostaglandin E2 a product of the conversion of arachidonic acid via the COX-2 pathway has been implicated in tumourigenesis through
1 promotion of angiogenesis
2 anti-apoptotic properties
3 increasing expression of matrix metalloproteinases and hence the ability of a tumour cell to undergo metastasis
4 altering the cytokine expression profile of cells
The class of eicosanoid synthesised will depend on the PUFA substrate Whilst arachidonic acid is converted to 2-series prostaglandins and 4-series leukotrienes EPA is converted to 3-series prostaglandins and 5-series leukotrienes Overall the latter eicosanoids are less potent as inflammatory mediators than those derived from arachidonic acid
Increasing daily intake of EPA the omega-3 PUFA analogue of arachidonic acid alters the balance between the cell content of these fatty acids This results in reduced production of the more active inflammatorytumourigenic products of arachidonic acid metabolism This is supported by the results of recent work at St Georges Hospital Medical School London In patients with a history of colonic adenomas daily dosing with a highly purified free-fatty acid form of the EPA produced a significant reduction in cell proliferation and increase in apoptosis in the colonic mucosa This preparation of EPA has the proprietary name Alfa and is referred to here as EPA
This proposed study will be based upon the randomised placebo-controlled National Cancer Institute sponsored study in which three groups of FAP patients were assigned to one of two doses of celecoxib a COX-2 inhibitor or placebo The results showed a reduction in the polyp burden of the group taking the higher 400mg twice daily bd dose However there is evidence to suggest that COX-2 inhibitors carry significant potential for side-effects Adopting a similar design EPA will be substituted for celecoxib in this randomised placebo-controlled trial comparing 2g EPA to placebo with reduction in polyp burden as the primary objective
FAP is an inherited susceptibility to diffuse colorectal adenomas and colorectal carcinoma occurring in close to 100 of unresected colons It is caused by a germline mutation in the Adenomatous Polyposis Coli APC gene located in the long arm of chromosome 5 To prevent cancer development it is recommended that patients with FAP undergo colectomy with ileo-anal or ileo-rectal anastomosis or colectomy and end-ileostomy at a socially convenient time before polyp progression to malignancy and before the age of 25 Patients with the attenuated FAP phenotype often associated with mutations at the 5 terminus exon 4 and proximally have fewer polyps and may often delay colectomy Patients with an ileo-rectal anastomosis are still susceptible to polyp formation in the remaining rectal stump and require 6 monthly check-ups with a flexible sigmoidoscope with removal of any polyps that develop Therefore an effective chemopreventative agent with a favourable side-effect profile would be of benefit to FAP patients with ileo-rectal anastomosis IRA and recurrent rectal polyps in addition to young adults who prefer to delay colectomy If such an agent were to be effective in FAP patients in the prevention of colonic polyps it may also be of benefit to the larger population of patients with sporadic colorectal adenomatous polyps who are also at risk of colorectal cancer
Colorectal polyps are thought at least in part to arise from an imbalance in the levels of cell proliferation and apoptosis natural cell death in the colonic mucosa It has been suggested that omega-3 polyunsaturated fatty acids PUFAs in fish oil can manipulate the high levels of colonic-mucosal cell proliferation rates associated with colonic adenomas
The rationale for this trial is based on the increasing evidence linking inflammatory processes and the development of a number of cancers including bowel cancer This has focused attention on the role of inflammatory mediators in the development of cancer In particular the family of eicosanoids including 2-series prostaglandins 4-series leukotrienes and thromboxanes produced through conversion of the omega-6 PUFA arachidonic acid via cyclo-oxygenase-2 COX-2 is believed to contribute to the physiological processes of inflammation and the development of tumours Prostaglandin E2 a product of the conversion of arachidonic acid via the COX-2 pathway has been implicated in tumourigenesis through
1 promotion of angiogenesis
2 anti-apoptotic properties
3 increasing expression of matrix metalloproteinases and hence the ability of a tumour cell to undergo metastasis
4 altering the cytokine expression profile of cells
The class of eicosanoid synthesised will depend on the PUFA substrate Whilst arachidonic acid is converted to 2-series prostaglandins and 4-series leukotrienes EPA is converted to 3-series prostaglandins and 5-series leukotrienes Overall the latter eicosanoids are less potent as inflammatory mediators than those derived from arachidonic acid
Increasing daily intake of EPA the omega-3 PUFA analogue of arachidonic acid alters the balance between the cell content of these fatty acids This results in reduced production of the more active inflammatorytumourigenic products of arachidonic acid metabolism This is supported by the results of recent work at St Georges Hospital Medical School London In patients with a history of colonic adenomas daily dosing with a highly purified free-fatty acid form of the EPA produced a significant reduction in cell proliferation and increase in apoptosis in the colonic mucosa This preparation of EPA has the proprietary name Alfa and is referred to here as EPA
This proposed study will be based upon the randomised placebo-controlled National Cancer Institute sponsored study in which three groups of FAP patients were assigned to one of two doses of celecoxib a COX-2 inhibitor or placebo The results showed a reduction in the polyp burden of the group taking the higher 400mg twice daily bd dose However there is evidence to suggest that COX-2 inhibitors carry significant potential for side-effects Adopting a similar design EPA will be substituted for celecoxib in this randomised placebo-controlled trial comparing 2g EPA to placebo with reduction in polyp burden as the primary objective
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None