Efficiency of Ursodesoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis Patients. URSOPAF
Overview
- Phase
- Phase 2
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- SPIGELMAN severity score of duodenal lesion after 2 years of follow-up
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •non-steroid anti-inflammatory drugs;
- •tamoxifen;
- •cholestyramine.
- •Pregnancy
- •Breast-feeding
Arms & Interventions
1
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
Intervention: Ursodeoxycholic acid (Drug)
2
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
SPIGELMAN severity score of duodenal lesion after 2 years of follow-up
Time Frame: Baseline, 1 and 2 years
Secondary Outcomes
- Cellular proliferation (Ki 67 and PCNA)(At the baseline, 1 and 2 years)
- Compliance to the treatment(Every 6 months during 2 years)
- Biliary acid profile(At the baseline, 1 and 2 years)