Prevention of Progression of Duodenal Adenomas in Patients With Familial Adenomatous Polyposis

Study Overview
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Brief Summary
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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.

Official Title
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Prevention of Progression of Duodenal Adenomas to Cancer in Patients With Familial Adenomatous Polyposis (FAP)

Conditions
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Familial Adenomatous Polyposis, Duodenal Neoplasms, Duodenal Polyps

Intervention / Treatment
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* Drug: Celecoxib
* Drug: Ursodeoxycholic acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Patients receive oral celecoxib twice daily and oral placebo twice daily | Drug: Celecoxib<br>* Celecoxib: 400mg twice daily, orally, 6 months<br>Drug: Placebo<br>* 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<br>|
| Experimental: Group 2<br>Patients receive oral celecoxib twice daily and oral ursodeoxycholic acid twice daily | Drug: Celecoxib<br>* Celecoxib: 400mg twice daily, orally, 6 months<br>Drug: Ursodeoxycholic acid<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cell proliferation, in normal mucosa and adenomas (if present) |  | Baseline, 6 months | 
| Biliary acid profile (if present) |  | Baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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