Clinical trial NCT00432913: Effect of 2 Doses of EPA on Apoptosis and Cell Proliferation on Colon Mucosa
Official title: The Effect of Two Dose Levels of Eicosapentaenoic Acid (EPA) on Apoptosis and Cell Proliferation in the Colonic Mucosa of Patients With a History of Colonic Polyps.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Adenomatous Polyps
Keywords: Eicosapentaenoic acid
EPA
EPA 99%
Fatty acid
omega-3
apoptosis
cell proliferation
colonic mucosa
polyps
adenomatous polyps
endoscopy
PUFA
Lead sponsor: S.L.A. Pharma AG
Sponsor class: INDUSTRY
First posted: 2007-02-08
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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%.
timeFrame: 3 months and 6 months
measure: 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%.
timeFrame: 3 months and 6 months
Secondary outcomes:
measure: To measure the tissue content of EPA in the colonic mucosa before, during and after treatment with EPA.
timeFrame: 3 months and 6 months
measure: To determine the safety and tolerability of EPA.
timeFrame: 3 months and 6 months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: S. Orsola Hospital
city: London
country: United Kingdom
facility: St. George's Hospital Medical School
Study officials:
affiliation: St. George's Hospital Medical School, London
name: Nicholas J West, MB BS FRCS
role: PRINCIPAL_INVESTIGATOR
References: