Effect of 2 Doses of EPA on Apoptosis and Cell Proliferation on Colon Mucosa - Full Text View

Sponsored by:	S.L.A. Pharma AG
Information provided by:	S.L.A. Pharma AG
ClinicalTrials.gov Identifier:	NCT00432913

Purpose

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.

Condition	Intervention	Phase
Adenomatous Polyps	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	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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.

Resource links provided by NLM:

MedlinePlus related topics: Colonic Polyps Endoscopy Urine and Urination

Drug Information available for: Docosahexaenoic acids Eicosapentaenoic acid

U.S. FDA Resources

Further study details as provided by S.L.A. Pharma AG:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	120
Study Start Date:	October 2006
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1g EPA per day: Active Comparator	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) Procedure: Endoscopy At baseline, month 3 and month 6. 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.
2g EPA per day: Active Comparator	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) Procedure: Endoscopy At baseline, month 3 and month 6. 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.
Placebo: Placebo Comparator	Procedure: Endoscopy At baseline, month 3 and month 6. 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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00432913

Locations

Italy
S. Orsola Hospital
Bologna, Italy, 40138
United Kingdom
St. George's Hospital Medical School
London, United Kingdom, SW17 0RE

Sponsors and Collaborators

S.L.A. Pharma AG

Investigators

Principal Investigator:

Nicholas J West, MB BS FRCS

St. George's Hospital Medical School, London

More Information

No publications provided

Study ID Numbers:	EPA/POL/02
Study First Received:	February 7, 2007
Last Updated:	October 16, 2008
ClinicalTrials.gov Identifier:	NCT00432913 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency; United Kingdom: Research Ethics Committee

Keywords provided by S.L.A. Pharma AG:

Eicosapentaenoic acid
EPA
EPA 99%
Fatty acid
omega-3
apoptosis

cell proliferation
colonic mucosa
polyps
adenomatous polyps
endoscopy
PUFA

Study placed in the following topic categories:

Pathological Conditions, Anatomical
Omega 3 Fatty Acid
Colonic Polyps
Polyps

Adenoma
Adenomatous Polyps
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Pathological Conditions, Anatomical
Neoplasms
Neoplasms by Histologic Type
Polyps

Adenoma
Adenomatous Polyps
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 02, 2009