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

Primary Purpose

Adenomatous Polyposis Coli, Familial

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Ursodeoxycholic acid
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenomatous Polyposis Coli, Familial focused on measuring Treatment of adenomas of the duodenum in FAP patients., Adenoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Saint-Antoine Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Cellular proliferation (Ki 67 and PCNA)
Biliary acid profile
Compliance to the treatment

Full Information

First Posted
August 23, 2005
Last Updated
July 28, 2009
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Axcan Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT00134758
Brief Title
Ursodeoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis (FAP) Patients
Official Title
Efficiency of Ursodesoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis Patients. URSOPAF
Study Type
Interventional

2. Study Status

Record Verification Date
July 2009
Overall Recruitment Status
Unknown status
Study Start Date
October 2004 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
October 2009 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Axcan Pharma

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenomatous Polyposis Coli, Familial
Keywords
Treatment of adenomas of the duodenum in FAP patients., Adenoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
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
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ursodeoxycholic acid
Other Intervention Name(s)
Delursan
Intervention Description
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 Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
SPIGELMAN severity score of duodenal lesion after 2 years of follow-up
Time Frame
Baseline, 1 and 2 years
Secondary Outcome Measure Information:
Title
Cellular proliferation (Ki 67 and PCNA)
Time Frame
At the baseline, 1 and 2 years
Title
Biliary acid profile
Time Frame
At the baseline, 1 and 2 years
Title
Compliance to the treatment
Time Frame
Every 6 months during 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yann RA Parc, M.D., Ph.D.
Organizational 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
Official's Role
Principal Investigator
Facility Information:
Facility Name
Saint-Antoine Hospital
City
Paris
ZIP/Postal Code
75012
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
2571019
Citation
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Citation
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Results Reference
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PubMed Identifier
6872780
Citation
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PubMed Identifier
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Citation
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PubMed Identifier
761204
Citation
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Citation
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Citation
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derived

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

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