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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
S.L.A. Pharma AG
ClinicalTrials.gov Identifier:
NCT00510692
First received: July 30, 2007
Last updated: August 6, 2014
Last verified: August 2014
  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
Drug: Placebo
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 (FAP) 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 Focal Area of the Rectum. [ Time Frame: 6 months compared to baseline. ] [ Designated as safety issue: No ]
    Absolute change in the number of polyps measured in a defined focal area of the rectum.


Secondary Outcome Measures:
  • Percentage Change in the Number of Polyps Measured in the Defined Focal Area of the Rectum. [ Time Frame: 6 months compared to baseline. ] [ Designated as safety issue: No ]
    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.

  • Change in Global Rectal Polyp Burden. [ Time Frame: 6 months compared to baseline. ] [ Designated as safety issue: No ]
    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.

  • Relative EPA Concentration of Total Free Fatty Acids in the Rectal Mucosa. [ Time Frame: 6 months compared to baseline. ] [ Designated as safety issue: No ]
    Relative EPA concentration of total free fatty acids in the rectal mucosa of subjects with FAP.

  • Number of Subjects With Adverse Events. [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: Yes ]
    Incidence of adverse events in each treatment group.


Enrollment: 58
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
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

  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 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
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):
Responsible Party: S.L.A. Pharma AG
ClinicalTrials.gov Identifier: NCT00510692     History of Changes
Other Study ID Numbers: EPA/POL/03
Study First Received: July 30, 2007
Results First Received: July 7, 2014
Last Updated: August 6, 2014
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
Adenoma
Adenomatous Polyps
Colonic Diseases
Colonic Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genetic Diseases, Inborn
Intestinal Diseases
Intestinal Neoplasms
Intestinal Polyposis
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplastic Syndromes, Hereditary

ClinicalTrials.gov processed this record on November 20, 2014