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

This study has been completed.
Sponsor:
Information provided by:
S.L.A. Pharma AG
ClinicalTrials.gov Identifier:
NCT00432913
First received: February 7, 2007
Last updated: October 16, 2008
Last verified: October 2008

February 7, 2007
October 16, 2008
October 2006
June 2008   (final data collection date for primary outcome 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%. [ Time Frame: 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%. [ Time Frame: 3 months and 6 months ]
To measure levels of apoptosis and proliferation levels in patients with a history of colonic adenomas, before and after treatment with EPA.
Complete list of historical versions of study NCT00432913 on ClinicalTrials.gov Archive Site
  • To measure the tissue content of EPA in the colonic mucosa before, during and after treatment with EPA. [ Time Frame: 3 months and 6 months ]
  • To determine the safety and tolerability of EPA. [ Time Frame: 3 months and 6 months ]
  • To measure the uptake of EPA into the colonic mucosa before and after treatment with EPA.
  • To determine the safety and tolerability of EPA.
Not Provided
Not Provided
 
Effect of 2 Doses of EPA on Apoptosis and Cell Proliferation on Colon Mucosa
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.

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Adenomatous Polyps
  • Drug: Eicosapentaenoic Acid (EPA)
    Either 2 x 500mg EPA capsules in the morning and evening (2g per day EPA) or 1 x 500mg EPA and 1 x placebo in the morning and evening (1g per day EPA)
    Other Name: ALFA
  • Procedure: Endoscopy
    At baseline, month 3 and month 6.
    Other Names:
    • Colonoscopy
    • Flexible sigmoidoscopy
  • Procedure: Biopsies taken
    9 biopsies taken for measurement of apoptosis (3 biopsies), cell proliferation (3 biopsies) and fatty acid levels (3 biopsies) at baseline, month 3 and month 6.
  • Procedure: Clinical chemistry
    Full blood count at baseline, month 3 and month 6.
  • Procedure: Haematology
    Urea and electrolytes, liver function tests, clotting profile and CRP at baseline, month 3 and month 6.
  • Procedure: Physical examination
    Including cardio-respiratory and abdominal examination at baseline, month 3 and month 6.
  • Procedure: Vital signs
    Height, weight, heart rate, blood pressure and temperature at baseline, month 3 and month 6.
  • Procedure: Urine pregnancy test
    For subjects of child-bearing potential, urine pregnancy test at baseline, month 3 and month 6.
  • Procedure: Completion of patient diary card
    Subjects are requested to complete when study medication is taken and in any new or unusual symptoms are experienced on a daily basis for 6 months.
  • Active Comparator: 1g EPA per day
    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
  • Active Comparator: 2g EPA per day
    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
  • Placebo Comparator: Placebo
    Interventions:
    • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
120
June 2008
June 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy,   United Kingdom
 
NCT00432913
EPA/POL/02
No
Not Provided
S.L.A. Pharma AG
Not Provided
Principal Investigator: Nicholas J West, MB BS FRCS St. George's Hospital Medical School, London
S.L.A. Pharma AG
October 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP