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

Study Overview
=================
Brief 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.

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.

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

Conditions
-----------------
Adenomatous Polyposis Coli, Familial

Intervention / Treatment
-----------------
* Drug: Ursodeoxycholic acid
* Drug: Placebo


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* 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<br>* Other names: Delursan;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SPIGELMAN severity score of duodenal lesion after 2 years of follow-up |  | Baseline, 1 and 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cellular proliferation (Ki 67 and PCNA) |  | At the baseline, 1 and 2 years | 
| Biliary acid profile |  | At the baseline, 1 and 2 years | 
| Compliance to the treatment |  | Every 6 months during 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adenoma, Treatment of adenomas of the duodenum in FAP patients.