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

NCT ID: NCT00134758

Last Updated: 2009-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-10-31

Study Completion Date

2009-10-31

Brief Summary

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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

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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.

Conditions

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Adenomatous Polyposis Coli, Familial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

Group Type EXPERIMENTAL

Ursodeoxycholic acid

Intervention Type DRUG

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

2

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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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 Type DRUG

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

Intervention Type DRUG

Other Intervention Names

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Delursan

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Axcan Pharma

INDUSTRY

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Department of clinical research and development

Principal Investigators

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Yann RA Parc, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Saint-Antoine Hospital

Paris, , France

Site Status

Countries

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France

References

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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. doi: 10.1016/s0140-6736(89)90840-4.

Reference Type BACKGROUND
PMID: 2571019 (View on PubMed)

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. doi: 10.1002/bjs.1800801244.

Reference Type BACKGROUND
PMID: 8298943 (View on PubMed)

Jarvinen HJ, Nyberg M, Peltokallio P. Biliary involvement in familial adenomatosis coli. Dis Colon Rectum. 1983 Aug;26(8):525-8. doi: 10.1007/BF02563746.

Reference Type BACKGROUND
PMID: 6872780 (View on PubMed)

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. doi: 10.1002/bjs.1800780318.

Reference Type BACKGROUND
PMID: 1850640 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 761204 (View on PubMed)

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. doi: 10.1016/s0140-6736(75)91556-1.

Reference Type BACKGROUND
PMID: 47015 (View on PubMed)

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. doi: 10.1136/gut.25.8.824.

Reference Type BACKGROUND
PMID: 6745720 (View on PubMed)

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. doi: 10.1016/s0140-6736(82)91810-4. No abstract available.

Reference Type BACKGROUND
PMID: 6121223 (View on PubMed)

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. doi: 10.1093/carcin/4.10.1239.

Reference Type BACKGROUND
PMID: 6616753 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7923119 (View on PubMed)

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. doi: 10.1053/jhep.2003.50311.

Reference Type BACKGROUND
PMID: 12830003 (View on PubMed)

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. doi: 10.1097/01.sla.0000114216.90947.f6.

Reference Type BACKGROUND
PMID: 15075655 (View on PubMed)

Parc Y, Desaint B, Flejou JF, Lefevre JH, Serfaty L, Vienne A, Kotti S, Simon T, Tiret E. The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous polyposis: a prospective randomized placebo-control trial. Colorectal Dis. 2012 Jul;14(7):854-60. doi: 10.1111/j.1463-1318.2011.02816.x.

Reference Type DERIVED
PMID: 21899713 (View on PubMed)

Other Identifiers

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AOM 03041

Identifier Type: -

Identifier Source: secondary_id

P030419

Identifier Type: -

Identifier Source: org_study_id

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