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

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Familial Adenomatous Polyposis Coli; FAP	Drug: Eicosapentanoic Acid (EPA); Procedure: Endoscopy; Procedure: Biopsies taken; Drug: Placebo	Phase 2; Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	58 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	A Two-Arm Chemoprevention Trial in Familial Adenomatous Polyposis (FAP) Coli Patients Using the Purified Free Fatty Acid, Eicosapentaenoic Acid
Study Start Date :	November 2006
Actual Primary Completion Date :	April 2008
Actual Study Completion Date :	April 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 2g/day Eicosapentanoic Acid (EPA); Eicosapentanenoic Acid (EPA) as the free fatty acid 2 capsules twice daily for 6 months. Endoscopy and biopsies taken as described under intervention.	Drug: Eicosapentanoic Acid (EPA); 2 x 500mg EPA capsules twice daily for 6 months; Other Name: ALFA Procedure: Endoscopy; Endoscopy with video and photographs at baseline and month 6.; Other Name: Endoscopy either Colonoscopy or Flexible sigmoidoscopy. Procedure: Biopsies taken; 9 biopsies taken at baseline and month 6 from the rectum of normal mucosa for analysis of apoptosis (3 biopsies), cell proliferation (3 biopsies) and mucosal fatty acid levels (3 biopsies). Two biopsies taken at baseline and month 6 from polyps for cell proliferation (1 biopsy) and apoptosis (1 biopsy).
Placebo Comparator: Placebo; Medium chain triglycerides 2 capsules twice daily for six months. Endoscopy and biopsies taken as described under intervention.	Procedure: Endoscopy; Endoscopy with video and photographs at baseline and month 6.; Other Name: Endoscopy either Colonoscopy or Flexible sigmoidoscopy. Procedure: Biopsies taken; 9 biopsies taken at baseline and month 6 from the rectum of normal mucosa for analysis of apoptosis (3 biopsies), cell proliferation (3 biopsies) and mucosal fatty acid levels (3 biopsies). Two biopsies taken at baseline and month 6 from polyps for cell proliferation (1 biopsy) and apoptosis (1 biopsy). Drug: Placebo; 2 x 500mg placebo capsules twice daily for 6 months

Outcome Measures

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Primary Outcome Measures :

1. Absolute Change in the Number of Polyps Measured in a Focal Area of the Rectum. [ Time Frame: 6 months compared to baseline. ]
   Absolute change in the number of polyps measured in a defined focal area of the rectum.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. Number of Subjects With Adverse Events. [ Time Frame: 6 months compared to baseline ]
   Incidence of adverse events in each treatment group.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Subjects must have a known diagnosis of Familial Adenomatous Polyposis (FAP) and have had a previous colectomy with ileo-rectal anastomosis.
• Males or females aged 18 and over
• If the participant is female and of child bearing potential, she agrees to participate in this study by providing written informed consent, has been using adequate contraception (e.g. abstinence, condom, Intra-uterine device (IUD), birth control pill, diaphragm and spermicidal gel combination) since her last menses and will use adequate contraception during the study, is not lactating, and agrees to undergo a serum pregnancy test at baseline and month 6. Sexually active males must agree to use an accepted method of contraception.
• Rectal polyp status: the subject has an endoscopically assessable rectal segment.
• Subjects must show a willingness to abstain from regular use of non-steroidal anti-inflammatory medication for the duration of the study. A cardioprotective dose of aspirin (75mg) will be permitted.
• Subjects must have provided written informed consent to participate.
• Subjects must have assessable rectal polyps post baseline flexible sigmoidoscopy.
• Subjects must have the following rectal polyp burden at the conclusion of the baseline endoscopy:
• Rectum - 3 or more quantifiable polyps ≥2mm diameter
• In the rectum quantifiable polyps are defined as being within a composite "cloverleaf" photograph that includes a tattoo.

Exclusion Criteria:

• Subjects who are due to undergo an anticipated colectomy within 8 months of randomisation
• History of invasive carcinoma in the past 5 years other than resected Dukes' A/B1 colon cancer or resected non-melanomatous skin cancer
• Partial or complete colectomy within 12 months prior to enrolment.
• History of pelvic radiation
• Subjects who are allergic to fish
• Subjects who have diabetes mellitus
• Subjects who are pregnant or breast-feeding
• Subjects taking aspirin or other non-steroidal anti-inflammatory drugs on a regular basis other than low dose (75 mg) cardioprotective dose.
• Subjects who have aspirin-sensitive asthma
• Subjects suffering from haemorrhagic disorders
• Subjects who are taking warfarin or other anticoagulants
• Subjects who have significant abnormalities on their screening blood tests
• Subjects taking lipid lowering medication
• Subjects with gastrointestinal malabsorptive disease
• Subjects with known or prior coagulopathy
• Subjects with uncontrolled hypercholesterolaemia
• Subjects who are taking other fish-oil supplements (e.g. cod liver oil) who are unwilling to stop them for the duration of the study. Subjects previously taking fish oil must have a washout period of 1 month prior to study enrolment.
• Subjects who are deemed mentally incompetent, or have a history of anorexia nervosa or bulimia
• Subjects with a history of alcohol or drug abuse, including laxative abuse which would render the subject unreliable.
• Subjects considered by their physician unlikely to be able to comply with the protocol.
• Subjects who have taken part in an experimental drug study in the preceding 3 months.
• Subjects who have a positive pregnancy test within 14 days prior to baseline visit.

Contacts and Locations

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Locations

United Kingdom
The Polyposis Registry, St. Mark's Hospital,
Harrow, Middlesex, United Kingdom, HA1 3UJ

Sponsors and Collaborators

S.L.A. Pharma AG

Investigators

Principal Investigator:	Nicholas J West, MB BS FRCS	The Polyposis Registry, St. Mark's Hospital,

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut. 2010 Jul;59(7):918-25. doi: 10.1136/gut.2009.200642. Epub 2010 Mar 26.

Responsible Party:	S.L.A. Pharma AG
ClinicalTrials.gov Identifier:	NCT00510692 History of Changes
Other Study ID Numbers:	EPA/POL/03
First Posted:	August 2, 2007
Results First Posted:	August 22, 2014
Last Update Posted:	August 22, 2014
Last Verified:	August 2014

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

Eicosapentaenoic Acid; EPA; EPA 99%; Fatty acid; omega-3; apoptosis; cell proliferation; colonic mucosa	polyp; Familial Adenomatous Polyposis Coli; FAP; resolvin; Ileo-rectal anastomosis; IRA; PUFA; Endoscopy

Additional relevant MeSH terms:

Colorectal Neoplasms; Nasopharyngeal Neoplasms; Adenomatous Polyposis Coli; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pharyngeal Neoplasms	Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Genetic Diseases, Inborn