Clinical Trial: Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Using EPA

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Two-Arm Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Patients Using the Purified Free Fatty Acid, Eicosapentaenoic Acid

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 Summary:

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
Sponsor: S.L.A. Pharma AG

Current Primary Outcome: Absolute Change in the Number of Polyps Measured in a Focal Area of the Rectum. [ Time Frame: 6 months compared to baseline. ]

Original Primary Outcome: Absolute change in the number of polyps measured in a defined focal area of the rectum. [ Time Frame: 6 months ]

Current Secondary Outcome:

• Percentage Change in the Number of Polyps Measured in the Defined Focal Area of the Rectum. [ Time Frame: 6 months compared to baseline. ]
  Percentage change in the number of polyps measured in the defined focal area of the rectum in subjects treated with EPA compared to subjects receiving placebo.
• Change in Global Rectal Polyp Burden. [ Time Frame: 6 months compared to baseline. ]
  Change in global rectal polyp burden in subjects treated with Eicosapentanoic Acid (EPA) compared to subjects receiving placebo. Each reviewer in the Polyp Video Scoring Committee assessed global colorectal polyp burden change as "better", "same as" or "worse". The qualitative assessment was assigned a score of +1 for "better", 0 for "same as" and -1 for "worse". Thereafter a mean overall reviewers score was calculated.
• Relative EPA Concentration of Total Free Fatty Acids in the Rectal Mucosa. [ Time Frame: 6 months compared to baseline. ]
  Relative EPA concentration of total free fatty acids in the rectal mucosa of subjects with FAP.
• Number of Subjects With Adverse Events. [ Time Frame: 6 months compared to baseline ]
  Incidence of adverse events in each treatment group.

Original Secondary Outcome:

• Percentage change in the number of polyps measured in the defined focal area of the rectum in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
• Actual and percentage change in the sum of the polyp diameters in the defined focal area of the rectum in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
• Change in global rectal polyp burden in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
• Levels of apoptosis in the rectal mucosa of subjects with FAP in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
• Levels of cell proliferation in the rectal mucosa of subjects with FAP in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
• Uptake of EPA and relative concentrations of free fatty acids in the rectal mucosa of subjects with FAP. [ Time Frame: 6 months ]
• Determine the safety and tolerability of EPA 99%. [ Time Frame: 6 months ]

Dates:
Date Received: July 30, 2007
Date Started: November 2006
Date Completion:
Last Updated: August 6, 2014
Last Verified: August 2014