Clinical trial NCT00808743: Prevention of Progression of Duodenal Adenomas in Patients With Familial Adenomatous Polyposis
Official title: Prevention of Progression of Duodenal Adenomas to Cancer in Patients With Familial Adenomatous Polyposis (FAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Familial Adenomatous Polyposis
Duodenal Neoplasms
Duodenal Polyps
Keywords: Familial adenomatous polyposis
Adenomatous Polyposis Coli
Digestive System Neoplasms
Gastrointestinal Disease
Intestinal disease
Intestinal neoplasms
Gastrointestinal neoplasms
Polyps
Adenoma
Adenomatous Polyps
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Genetic Diseases, Inborn
Chemoprevention
Celecoxib
Ursodeoxycholic acid
Anti-Inflammatory agents, Non-Steroidal
Cyclooxygenase Inhibitors
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2008-12-16
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Duodenal carcinomas are the leading cause of mortality in patients with Familial Adenomatous Polyposis (FAP) who underwent prophylactic colorectal surgery. The purpose of this study is to determine wether celecoxib combined with ursodeoxycholic acid is an effective chemoprevention strategy to influence the progression of duodenal adenomas to carcinomas in patients with FAP.


Eligibility criteria: Inclusion Criteria:

* Patients with Familial adenomatous Polyposis: APC-mutation identified or more than 100 colorectal polyps on diagnosis
* Spigelman score of duodenal adenoma equal to II or III

Exclusion Criteria:

* Incapability of signing informed consent
* Active gastric or duodenal ulcer, gastrointestinal bleeding
* Cardiovascular disease or risk:

  * Congestive cardiac failure: NYHA class II to IV
  * Proven ischemic heart disease and/or cerebrovascular disease
  * Risk factors: hypertension, hyperlipidaemia, diabetes mellitus, family history of cardiovascular events (≥2 first degree family members \<55 years)
* Renal dysfunction: creatinine clearance below 50mL/min
* Liver dysfunction: albumin below 25 g/L or Child-Pugh-score equal to or below 10
* Known allergic reaction to sulfonamides, NSAIDs or ursodeoxycholic acid
* Use of NSAIDs or ursodeoxycholic acid for more than 1 week during the 6 months prior to the start of the study
* Use of lithium
* Symptomatic gallstones
* Inflammatory bowel disease
* (Possible) pregnancy or breast feeding

Primary outcomes:
measure: Change in number and size of duodenal adenomas (assessed directly and by evaluation of video and photographic material from endoscopic procedures)
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Cell proliferation, in normal mucosa and adenomas (if present)
timeFrame: Baseline, 6 months
measure: Biliary acid profile (if present)
timeFrame: Baseline, 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: University Medical Center St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: University Medical Center St. Radboud Nijmegen, The Netherlands
name: Fokko M Nagengast, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center St. Radboud Nijmegen, The Netherlands
name: Bjorn WH van Heumen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center St Radboud Nijmegen, The Netherlands
name: Wilbert HM Peters, Ph D
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center St Radboud Nijmegen, The Netherlands
name: Ellen Kampman, Ph D
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Heumen BW, Roelofs HM, te Morsche RH, Nagengast FM, Peters WH. Duodenal mucosal risk markers in patients with familial adenomatous polyposis: effects of celecoxib/ursodeoxycholic acid co-treatment and comparison with patient controls. Orphanet J Rare Dis. 2013 Nov 19;8:181. doi: 10.1186/1750-1172-8-181.
citation: van Heumen BW, Roelofs HM, Vink-Borger ME, Dekker E, Mathus-Vliegen EM, Dees J, Koornstra JJ, Langers AM, Nagtegaal ID, Kampman E, Peters WH, Nagengast FM. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial. Orphanet J Rare Dis. 2013 Aug 6;8:118. doi: 10.1186/1750-1172-8-118.