Ursodeoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis (FAP) Patients - Full Text View

Sponsor:	Assistance Publique - Hôpitaux de Paris
Collaborator:	Axcan Pharma
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00134758

Purpose

Malignant transformation of adenomas of the duodenum is now the leading cause of death in familial adenomatous polyposis (FAP) patients who had a restorative proctocolectomy. Ursodeoxycholic acid (UDCA) modifies the biliary acid profile and could reduce the severity of duodenal adenomas and prevent such transformation.

Condition	Intervention	Phase
Adenomatous Polyposis Coli, Familial	Drug: Ursodeoxycholic acid Drug: Placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Efficiency of Ursodesoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis Patients. URSOPAF

Resource links provided by NLM:

Genetics Home Reference related topics: familial adenomatous polyposis

Drug Information available for: Ursodeoxycholic acid

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

SPIGELMAN severity score of duodenal lesion after 2 years of follow-up [ Time Frame: Baseline, 1 and 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Cellular proliferation (Ki 67 and PCNA) [ Time Frame: At the baseline, 1 and 2 years ] [ Designated as safety issue: No ]
Biliary acid profile [ Time Frame: At the baseline, 1 and 2 years ] [ Designated as safety issue: No ]
Compliance to the treatment [ Time Frame: Every 6 months during 2 years ] [ Designated as safety issue: No ]

Enrollment:	90
Study Start Date:	October 2004
Estimated Study Completion Date:	October 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Ursodeoxycholic acid during 2 years : between 40 and 50 kg : 500 mg/day between 51 and 75 kg : 750 mg/day between 76 and 100 kg : 1000 mg/day	Drug: Ursodeoxycholic acid During 2 years : between 40 and 50 kg : 500 mg/day between 51 and 75 kg : 750 mg/day between 76 and 100 kg : 1000 mg/day
2: Placebo Comparator	Drug: Placebo During 2 years : between 40 and 50 kg : 2 tabs/day between 51 and 75 kg : 3 tabs/day between 76 and 100 kg : 4 tabs/day

Detailed Description:

We designed a randomized double blinded study to evaluate the efficiency of UDCA in the treatment of duodenal adenomas. One hundred patients are planned to be included. Fifty will receive UDCA and fifty a placebo. Three duodenoscopies are planned: one before inclusion, one at the end of the first year of follow-up and one after two years of follow-up at the end of the protocol. These duodenoscopies are associated to endoscopies of the ileal reservoir performed at the time of restorative proctocolectomy and are recorded numerically. Severity of the duodenal adenomas are evaluated according to the SPIGELMAN score. Patients are seen every 6 months. Before each endoscopy, blood samples are collected for biliary acid profile analysis. Moreover, during endoscopies, duodenal fluid and ileal fluid are collected for biliary acid profile analysis, also.

At the end of the follow-up of the last patients included (nov 2008), biliary acid profile analysis will be performed and statistical analysis of the results will be performed.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients between 18 and 65 years of age
Weight less than or equal to 100 kg
Restorative proctocolectomy
Activated protein C (APC) mutation identified or more than 100 polyps on the colectomy specimen
SPIGELMAN score of duodenal adenoma greater than or equal to 1
Efficient contraceptive treatment for pre-menopausal women
Cooperative patient
Signed consent
Social security insurance

Exclusion Criteria:

SPIGELMAN score of duodenal adenoma equal to 4 with severe dysplasia
Hepatic disease
Intermesenteric desmoid tumour
Any severe disease
Daily use during the last 3 months of:
- aspirin;
- non-steroid anti-inflammatory drugs;
- tamoxifen;
- cholestyramine.
Pregnancy
Breast-feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00134758

Locations

France
Saint-Antoine Hospital
Paris, France, 75012

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Axcan Pharma

Investigators

Principal Investigator:

Yann RA Parc, M.D., Ph.D.

Department of Digestive Surgery, Saint-Antoine Hospital, Hospital of Paris (AP/HP), Pierre et Marie Curie University, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France

More Information

Publications:

Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5.

Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK. Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg. 1993 Dec;80(12):1618-9.

Jarvinen HJ, Nyberg M, Peltokallio P. Biliary involvement in familial adenomatosis coli. Dis Colon Rectum. 1983 Aug;26(8):525-8.

Spigelman AD, Owen RW, Hill MJ, Phillips RK. Biliary bile acid profiles in familial adenomatous polyposis. Br J Surg. 1991 Mar;78(3):321-5.

Mower HF, Ray RM, Shoff R, Stemmermann GN, Nomura A, Glober GA, Kamiyama S, Shimada A, Yamakawa H. Fecal bile acids in two Japanese populations with different colon cancer risks. Cancer Res. 1979 Feb;39(2 Pt 1):328-31.

Hill MJ, Drasar BS, Williams RE, Meade TW, Cox AG, Simpson JE, Morson BC. Faecal bile-acids and clostridia in patients with cancer of the large bowel. Lancet. 1975 Mar 8;1(7906):535-9.

Tanida N, Hikasa Y, Shimoyama T, Setchell KD. Comparison of faecal bile acid profiles between patients with adenomatous polyps of the large bowel and healthy subjects in Japan. Gut. 1984 Aug;25(8):824-32.

van der Werf SD, Nagengast FM, van Berge Henegouwen GP, Huijbregts AW, van Tongeren JH. Colonic absorption of secondary bile-acids in patients with adenomatous polyps and in matched controls. Lancet. 1982 Apr 3;1(8275):759-62. No abstract available.

Wilpart M, Mainguet P, Maskens A, Roberfroid M. Structure-activity relationship amongst biliary acids showing comutagenic activity towards 1,2-dimethylhydrazine. Carcinogenesis. 1983 Oct;4(10):1239-41.

Earnest DL, Holubec H, Wali RK, Jolley CS, Bissonette M, Bhattacharyya AK, Roy H, Khare S, Brasitus TA. Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer Res. 1994 Oct 1;54(19):5071-4.

Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE, Poupon R. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology. 2003 Jul;38(1):203-9.

Parc Y, Piquard A, Dozois RR, Parc R, Tiret E. Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy. Ann Surg. 2004 Mar;239(3):378-82.

Responsible Party:	Department of clinical research and development ( Christophe Aucan )
Study ID Numbers:	P030419, AOM 03041
Study First Received:	August 23, 2005
Last Updated:	July 28, 2009
ClinicalTrials.gov Identifier:	NCT00134758 History of Changes
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Treatment of adenomas of the duodenum in FAP patients.
Adenoma

Additional relevant MeSH terms:

Intestinal Polyposis
Neoplasms by Histologic Type
Digestive System Neoplasms
Gastrointestinal Diseases
Adenomatous Polyposis Coli
Colonic Diseases
Gastrointestinal Agents
Intestinal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Ursodeoxycholic Acid
Neoplasms

Digestive System Diseases
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Therapeutic Uses
Cholagogues and Choleretics
Gastrointestinal Neoplasms
Adenoma
Colonic Neoplasms
Adenomatous Polyps
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2009