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Prevention of Progression of Duodenal Adenomas in Patients With Familial Adenomatous Polyposis (PreDuoFAP)

Primary Purpose

Familial Adenomatous Polyposis, Duodenal Neoplasms, Duodenal Polyps

Status

Completed

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

Celecoxib

Ursodeoxycholic acid

Placebo

About this trial

This is an interventional prevention trial for Familial Adenomatous Polyposis focused on measuring 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

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Academic Medical Center
University Medical Center
Leiden University Medical Center
University Medical Center St. Radboud
Erasmus Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Group 1

Group 2

Arm Description

Patients receive oral celecoxib twice daily and oral placebo twice daily

Patients receive oral celecoxib twice daily and oral ursodeoxycholic acid twice daily

Outcomes

Primary Outcome Measures

Change in number and size of duodenal adenomas (assessed directly and by evaluation of video and photographic material from endoscopic procedures)

Secondary Outcome Measures

Cell proliferation, in normal mucosa and adenomas (if present)

Biliary acid profile (if present)

Full Information

NCT ID

NCT00808743

First Posted

December 15, 2008

Last Updated

May 15, 2013

Sponsor

Radboud University Medical Center

Collaborators

Dutch Cancer Society

1. Study Identification

Unique Protocol Identification Number

NCT00808743

Brief Title

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

Acronym

PreDuoFAP

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2010

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

July 2011 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radboud University Medical Center

Collaborators

Dutch Cancer Society

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Active Comparator

Arm Description

Patients receive oral celecoxib twice daily and oral placebo twice daily

Arm Title

Group 2

Arm Type

Experimental

Arm Description

Patients receive oral celecoxib twice daily and oral ursodeoxycholic acid twice daily

Intervention Type

Drug

Intervention Name(s)

Celecoxib

Intervention Description

Celecoxib: 400mg twice daily, orally, 6 months

Intervention Type

Drug

Intervention Name(s)

Ursodeoxycholic acid

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in number and size of duodenal adenomas (assessed directly and by evaluation of video and photographic material from endoscopic procedures)

Time Frame

Baseline, 6 months

Secondary Outcome Measure Information:

Title

Cell proliferation, in normal mucosa and adenomas (if present)

Time Frame

Baseline, 6 months

Title

Biliary acid profile (if present)

Time Frame

Baseline, 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fokko M Nagengast, MD, Ph D

Organizational Affiliation

University Medical Center St. Radboud Nijmegen, The Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Bjorn WH van Heumen, MD

Organizational Affiliation

University Medical Center St. Radboud Nijmegen, The Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Wilbert HM Peters, Ph D

Organizational Affiliation

University Medical Center St Radboud Nijmegen, The Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ellen Kampman, Ph D

Organizational Affiliation

University Medical Center St Radboud Nijmegen, The Netherlands

Official's Role

Principal Investigator

Facility Information:

Facility Name

Academic Medical Center

City

Amsterdam

Country

Netherlands

Facility Name

University Medical Center

City

Groningen

Country

Netherlands

Facility Name

Leiden University Medical Center

City

Leiden

Country

Netherlands

Facility Name

University Medical Center St. Radboud

City

Nijmegen

Country

Netherlands

Facility Name

Erasmus Medical Center

City

Rotterdam

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

24245549

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.

Results Reference

derived

PubMed Identifier

23919274

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.

Results Reference

derived

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

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