Effect of 2 Doses of EPA on Apoptosis and Cell Proliferation on Colon Mucosa

Phase 2

Completed

• Conditions: Adenomatous Polyps
• Interventions: Drug: Eicosapentaenoic Acid (EPA); Procedure: Endoscopy; Procedure: Biopsies taken; Procedure: Clinical chemistry; Procedure: Haematology; Procedure: Physical examination; Procedure: Vital signs; Procedure: Urine pregnancy test; Procedure: Completion of patient diary card

• Registration Number: NCT00432913
• Lead Sponsor: S.L.A. Pharma AG

Brief Summary

The purpose of this study is to determine the effect of two doses purified EPA (an omega-3 fatty acid), on apoptosis (natural cell death) and cell proliferation (formation of new cells) in the lining of the colon for patients with a history of colonic polyps.

Detailed Description

Colorectal cancer is generally accepted to develop from changes within colonic adenomatous polyps. More than 90% of new large bowel cancers arise sporadically. The molecular events leading to the development of colorectal cancer from polyps are characterised by an imbalance in cell proliferation (formation of new cells) and apoptosis (natural cell death) from changes in the genes involved in normal colon cells.

Recent work at St George's Hospital Medical School, London, has shown significant beneficial effects on cell proliferation and apoptosis rates in the lining of the colon in subjects with a history of colonic adenomas using a highly purified, free-fatty acid form of eicosapentaenoic acid (EPA).

Comparator(s): 2g EPA per day for 6 months and 1g EPA per day for 6 months will be compared against placebo for 6 months.

Study Timeline

• Study Start: 2006-10
• Study First Submitted: 2007-02-07
• Study First Submitted QC: 2007-02-07
• Study First Posted: 2007-02-08
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Status Verified: 2008-10
• Last Update Submitted: 2008-10-16
• Last Update Posted: 2008-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Males or females aged over 18
• Patients of child-bearing potential must demonstrate a negative pregnancy test at screening, and should use a reliable form of contraception during the trial and for 1 month afterwards, e.g:
• Oral contraceptive + condom
• Intra-uterine device (IUD)+ condom
• Diaphragm with spermicide + condom
• Male partners of women of child bearing potential should use a reliable form of contraception during the trial and for 1 month afterwards, e.g:
• Oral contraceptive + condom
• Intra-uterine device (IUD)+ condom
• Diaphragm with spermicide + condom
• Patients must have a known history of colorectal adenomata and be under clinical follow-up for these, or be found to have one or more of these at the time of colonoscopy
• Patients must have provided written informed consent to participate

Exclusion Criteria

• Patients who are allergic to fish
• Patients who have diabetes mellitus
• Patients who are pregnant or breast-feeding
• Patients taking aspirin or other non-steroidal anti-inflammatory drugs on a regular basis
• Patients who have aspirin-sensitive asthma
• Patients suffering from haemorrhagic disorders
• Patients who are taking warfarin or other anticoagulants
• Patients who have significant abnormalities on their screening blood tests
• Patients taking lipid lowering medication
• Patients with known inflammatory bowel disease (IBD), or previously unknown IBD until discovered at the time of their colonoscopy
• Patients with gastrointestinal malabsorptive disease
• Patients belonging to a known polyposis syndrome (e.g. FAP, HNPCC)
• Patients with a previous colonic resection for colorectal cancer
• Patients who are taking other fish-oil supplements (e.g. cod liver oil) who are unwilling to stop them for the duration of the study
• Patients who are deemed mentally incompetent, or have a history of anorexia nervosa or bulimia
• Patients with a history of alcohol or drug abuse, including laxative abuse
• Patients considered by their physician unlikely to be able to comply with the protocol.
• Patients who have taken part in an experimental drug study in the preceding 2 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1g EPA per day	Eicosapentaenoic Acid (EPA)	-
1g EPA per day	Endoscopy	-
1g EPA per day	Biopsies taken	-
1g EPA per day	Clinical chemistry	-
1g EPA per day	Haematology	-
1g EPA per day	Physical examination	-
1g EPA per day	Vital signs	-
2g EPA per day	Biopsies taken	-
2g EPA per day	Clinical chemistry	-
2g EPA per day	Haematology	-
2g EPA per day	Physical examination	-
2g EPA per day	Completion of patient diary card	-
1g EPA per day	Urine pregnancy test	-
1g EPA per day	Completion of patient diary card	-
2g EPA per day	Eicosapentaenoic Acid (EPA)	-
2g EPA per day	Endoscopy	-
2g EPA per day	Vital signs	-
2g EPA per day	Urine pregnancy test	-
Placebo	Endoscopy	-
Placebo	Biopsies taken	-
Placebo	Clinical chemistry	-
Placebo	Haematology	-
Placebo	Physical examination	-
Placebo	Vital signs	-
Placebo	Urine pregnancy test	-
Placebo	Completion of patient diary card	-

Primary Outcome Measures

Name	Time	Method
To measure levels of apoptosis in the normal colonic mucosa in subjects with a history of colonic adenomas, before and after treatment with EPA 99%.	3 months and 6 months
To measure levels of cell proliferation in the normal colonic mucosa in subjects with a history of colonic adenomas, before and after treatment with EPA 99%.	3 months and 6 months

Secondary Outcome Measures

Name	Time	Method
To measure the tissue content of EPA in the colonic mucosa before, during and after treatment with EPA.	3 months and 6 months
To determine the safety and tolerability of EPA.	3 months and 6 months

Trial Locations

Locations (2)

St. George's Hospital Medical School; 🇬🇧 London, United Kingdom

S. Orsola Hospital; 🇮🇹 Bologna, Italy