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

Condition(s) targeted: Adenomatous Polyposis Coli

Intervention: Ursodeoxycholic acid (Drug); Placebo (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Yann RA Parc, M.D., Ph.D., Principal Investigator, Affiliation: 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

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: SPIGELMAN severity score of duodenal lesion after 2 years of follow-up

Secondary outcome:

Cellular proliferation (Ki 67 and PCNA)

Biliary acid profile

Compliance to the treatment

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Saint-Antoine Hospital, Paris 75012, France

Related publications:

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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.

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Starting date: October 2004
Ending date: May 2007
Last updated: June 4, 2008