Chemoprevention Trial in Familial Adenomatous Polyposis Coli Using EPA

This study has been completed.
Sponsor:
Information provided by:
S.L.A. Pharma AG
ClinicalTrials.gov Identifier:
NCT00510692
First received: July 30, 2007
Last updated: October 16, 2008
Last verified: October 2008
  Purpose

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 Intervention Phase
Familial Adenomatous Polyposis Coli
FAP
Drug: Eicosapentanoic 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
Procedure: Peripheral blood sample
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Two-Arm Chemoprevention Trial in Familial Adenomatous Polyposis Coli Patients Using the Purified Free Fatty Acid, Eicosapentaenoic Acid

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Absolute change in the number of polyps measured in a defined focal area of the rectum. [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Percentage change in the number of polyps measured in the defined focal area of the rectum in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
  • Actual and percentage change in the sum of the polyp diameters in the defined focal area of the rectum in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
  • Change in global rectal polyp burden in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
  • Levels of apoptosis in the rectal mucosa of subjects with FAP in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
  • Levels of cell proliferation in the rectal mucosa of subjects with FAP in subjects treated with EPA 99% compared to subjects receiving placebo. [ Time Frame: 6 months ]
  • Uptake of EPA and relative concentrations of free fatty acids in the rectal mucosa of subjects with FAP. [ Time Frame: 6 months ]
  • Determine the safety and tolerability of EPA 99%. [ Time Frame: 6 months ]

Enrollment: 63
Study Start Date: November 2006
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 2g/day EPA 99% Drug: Eicosapentanoic Acid (EPA)
2 x 500mg EPA capsules twice daily for 6 months
Other Name: ALFA
Procedure: Endoscopy
With video and photographs at baseline and month 6.
Other Names:
  • Colonoscopy
  • 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).
Procedure: Clinical Chemistry
Urea and electrolytes, liver function, clotting profile, and CRP at baseline and month 6.
Procedure: Haematology
Blood count at baseline and month 6.
Procedure: Physical examination
Including cardio-respiratory and abdominal examination at baseline and month 6.
Procedure: Vital signs
Height, weight, heart rate, blood pressure and temperature at baseline and month 6.
Procedure: Urine pregnancy test
For females of child-bearing potential, urine pregnancy test at baseline and month 6.
Procedure: Completion of patient diary card
Subjects are requested to record when doses of study medication are taken and if any new or unusual symptoms are experienced daily for 6 months.
Procedure: Peripheral blood sample
Peripheral blood sample for lipid and resolvin levels at baseline and month 6.
Placebo Comparator: Placebo Procedure: Endoscopy
With video and photographs at baseline and month 6.
Other Names:
  • Colonoscopy
  • 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).
Procedure: Clinical Chemistry
Urea and electrolytes, liver function, clotting profile, and CRP at baseline and month 6.
Procedure: Haematology
Blood count at baseline and month 6.
Procedure: Physical examination
Including cardio-respiratory and abdominal examination at baseline and month 6.
Procedure: Vital signs
Height, weight, heart rate, blood pressure and temperature at baseline and month 6.
Procedure: Urine pregnancy test
For females of child-bearing potential, urine pregnancy test at baseline and month 6.
Procedure: Completion of patient diary card
Subjects are requested to record when doses of study medication are taken and if any new or unusual symptoms are experienced daily for 6 months.
Procedure: Peripheral blood sample
Peripheral blood sample for lipid and resolvin levels at baseline and month 6.

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Subjects must have a known diagnosis of 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, 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00510692

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

No publications provided by S.L.A. Pharma AG

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00510692     History of Changes
Other Study ID Numbers: EPA/POL/03
Study First Received: July 30, 2007
Last Updated: October 16, 2008
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
polyp
Familial Adenomatous Polyposis Coli
FAP
resolvin
Ileo-rectal anastomosis
IRA
PUFA
Endoscopy

Additional relevant MeSH terms:
Adenomatous Polyposis Coli
Adenomatous Polyps
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Neoplasms
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Intestinal Polyposis
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 20, 2014