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

NCT00134758 | Unknown Phase 2 DMC

• 2 other identifiers: P030419AOM 03041
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenomatous Polyposis Coli, Familial

Keywords

Treatment of adenomas of the duodenum in FAP patients.; Adenoma

Outcome Measures

Primary Outcomes (1)

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

  Baseline, 1 and 2 years

Secondary Outcomes (3)

• 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

Study Arms (2)

1

EXPERIMENTAL

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

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ursodeoxycholic acid 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

Also known as: Delursan

1

Placebo 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

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Axcan Pharma: collaborator

Study Sites (1)

Saint-Antoine Hospital

Paris, 75012, France

Location

Related Publications (13)

• 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.

  PMID: 2571019 BACKGROUND

• 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.

  PMID: 8298943 BACKGROUND

• 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.

  PMID: 6872780 BACKGROUND

• 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.

  PMID: 1850640 BACKGROUND

• 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.

  PMID: 761204 BACKGROUND

• 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.

  PMID: 47015 BACKGROUND

• 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.

  PMID: 6745720 BACKGROUND

• 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.

  PMID: 6121223 BACKGROUND

• 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.

  PMID: 6616753 BACKGROUND

• 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.

  PMID: 7923119 BACKGROUND

• 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.

  PMID: 12830003 BACKGROUND

• 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.

  PMID: 15075655 BACKGROUND

• 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.

  PMID: 21899713 DERIVED

MeSH Terms

Conditions

Adenomatous Polyposis Coli; Adenoma

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Yann RA Parc, M.D., Ph.D.

  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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 23, 2005
• First Posted: August 25, 2005
• Study Start: October 1, 2004
• Primary Completion: June 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 29, 2009

Record last verified: 2009-07

Locations

FR (1)