Duodenal Neoplasms, Duodenal Polyps, Familial Adenomatous Polyposis
Conditions
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
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.
Interventions
DRUGCelecoxib
Celecoxib: 400mg twice daily, orally, 6 months
DRUGUrsodeoxycholic acid
Ursodeoxycholic acid: orally, 6 months, dosage based on body weight: below 50 kg: 1000mg, divided in two daily doses; 50-70 kg: 1500mg, divided in two daily doses; over 70 kg: 2000mg, divided in two daily doses
DRUGPlacebo
Placebo: orally, 6 months, dosage based on body weight: below 50 kg: 1000mg, divided in two daily doses; 50-70 kg: 1500mg, divided in two daily doses; over 70 kg: 2000mg, divided in two daily doses
Sponsors
Dutch Cancer Society
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in number and size of duodenal adenomas (assessed directly and by evaluation of video and photographic material from endoscopic procedures) | Baseline, 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Cell proliferation, in normal mucosa and adenomas (if present) | Baseline, 6 months |
| Biliary acid profile (if present) | Baseline, 6 months |
Countries
Netherlands
Outcome results
None listed