Ursodeoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis (FAP) Patients

Adenomatous Polyposis Coli, Familial Clinical Trial

Official title:

Efficiency of Ursodesoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis Patients. URSOPAF

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00134758
• Other study ID #: P030419
• Secondary ID: AOM 03041
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: August 23, 2005
• Last updated: July 28, 2009
• Start date: October 2004
• Est. completion date: October 2009

Study information

• Verified date: July 2009
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: October 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenoma
• Adenomatous Polyposis Coli
• Adenomatous Polyposis Coli, Familial

Intervention

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
• 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

Locations

Country	Name	City	State
France	Saint-Antoine Hospital	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Axcan Pharma

Country where clinical trial is conducted

France, 

References & Publications (12)

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SPIGELMAN severity score of duodenal lesion after 2 years of follow-up		Baseline, 1 and 2 years	No
Secondary	Cellular proliferation (Ki 67 and PCNA)		At the baseline, 1 and 2 years	No
Secondary	Biliary acid profile		At the baseline, 1 and 2 years	No
Secondary	Compliance to the treatment		Every 6 months during 2 years	No